Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs.

PubMed

Maeda, Kojiro; Kaneko, Masayuki; Narukawa, Mamoru; Arato, Teruyo

2017-08-23

The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future.

The development and psychometric testing of a theory-based instrument to evaluate nurses' perception of clinical reasoning competence.

PubMed

Liou, Shwu-Ru; Liu, Hsiu-Chen; Tsai, Hsiu-Min; Tsai, Ying-Huang; Lin, Yu-Ching; Chang, Chia-Hao; Cheng, Ching-Yu

2016-03-01

The purpose of the study was to develop and psychometrically test the Nurses Clinical Reasoning Scale. Clinical reasoning is an essential skill for providing safe and quality patient care. Identifying pre-graduates' and nurses' needs and designing training courses to improve their clinical reasoning competence becomes a critical task. However, there is no instrument focusing on clinical reasoning in the nursing profession. Cross-sectional design was used. This study included the development of the scale, a pilot study that preliminary tested the readability and reliability of the developed scale and a main study that implemented and tested the psychometric properties of the developed scale. The Nurses Clinical Reasoning Scale was developed based on the Clinical Reasoning Model. The scale includes 15 items using a Likert five-point scale. Data were collected from 2013-2014. Two hundred and fifty-one participants comprising clinical nurses and nursing pre-graduates completed and returned the questionnaires in the main study. The instrument was tested for internal consistency and test-retest reliability. Its validity was tested with content, construct and known-groups validity. One factor emerged from the factor analysis. The known-groups validity was confirmed. The Cronbach's alpha for the entire instrument was 0·9. The reliability and validity of the Nurses Clinical Reasoning Scale were supported. The scale is a useful tool and can be easily administered for the self-assessment of clinical reasoning competence of clinical nurses and future baccalaureate nursing graduates. Study limitations and further recommendations are discussed. © 2015 John Wiley & Sons Ltd.

Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines.

PubMed

Maclennan, Sara Jane; Maclennan, Steven J; Imamura, Mari; Omar, Muhammad Imran; Vale, Luke; Lam, Thomas; Royle, Pamela; Royle, Justine; Swami, Satchi; Pickard, Rob; McClinton, Sam; Griffiths, T R Leyshon; Dahm, Philipp; N'dow, James

2011-06-01

Making healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare. This paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups. The development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer. The process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties.

Strengthening the career development of clinical translational scientist trainees: a consensus statement of the Clinical Translational Science Award (CTSA) Research Education and Career Development Committees.

PubMed

Meyers, Frederick J; Begg, Melissa D; Fleming, Michael; Merchant, Carol

2012-04-01

The challenges for scholars committed to successful careers in clinical and translational science are increasingly well recognized. The Education and Career Development (EdCD) of the national Clinical and Translational Science Award consortium gathered thought leaders to propose sustainable solutions and an agenda for future studies that would strengthen the infrastructure across the spectrum of pre- and postdoctoral, MD and PhD, scholars. Six consensus statements were prepared that include: (1) the requirement for career development of a qualitatively different investigator; (2) the implications of interdisciplinary science for career advancement including institutional promotion and tenure actions that were developed for discipline-specific accomplishments; (3) the need for long-term commitment of institutions to scholars; (4) discipline-specific curricula are still required but curricula designed to promote team work and interdisciplinary training will promote innovation; (5) PhD trainees have many pathways to career satisfaction and success; and (6) a centralized infrastructure to enhance and reward mentoring is required. Several themes cut across all of the recommendations including team science, innovation, and sustained institutional commitment. Implied themes include an effective and diverse job force and the requirement for a well-crafted public policy that supports continued investments in science education. © 2012 Wiley Periodicals, Inc.

Cross-sector sponsorship of research in eosinophilic esophagitis: a collaborative model for rational drug development in rare diseases.

PubMed

Fiorentino, Robert; Liu, Gumei; Pariser, Anne R; Mulberg, Andrew E

2012-09-01

Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood disorder, and assessment tools to accurately determine disease activity, remission, and natural history have long been inadequate. Clinical outcome end points able to assess the effectiveness of candidate therapeutic agents in clinical trials have been a particular deficiency and are urgently needed. With no approved therapy available to patients and with the prevalence of EoE on the increase, collaborative approaches to drug development are becoming ever more important. We describe a collaborative effort mobilized across institutions, including both the public and private sectors, that was initiated within the past 18 months expressly to address the need for further clinical research into the cause and treatment of EoE. Collaborators include the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition; the International Gastrointestinal Eosinophilic Researchers; and the US Food and Drug Administration. This effort has resulted in the elucidation of several parameters essential for effective EoE registration trials, including the need for clinically meaningful end points that measure changes in clinical symptoms in addition to the assessment of intraepithelial mucosal eosinophilia. The development and use of biomarkers, particularly in early-phase drug development, have become an important focus for investigations that might reduce clinical reliance on serial invasive monitoring. The concerted efforts described here to develop rational therapeutics and drug development paradigms in EoE also appear to provide a model for effective collaboration in the context of drug development for rare diseases and perhaps more generally for public health initiatives. Published by Mosby, Inc.

Development of job standards for clinical nutrition therapy for dyslipidemia patients.

PubMed

Kang, Min-Jae; Seo, Jung-Sook; Kim, Eun-Mi; Park, Mi-Sun; Woo, Mi-Hye; Ju, Dal-Lae; Wie, Gyung-Ah; Lee, Song-Mi; Cha, Jin-A; Sohn, Cheong-Min

2015-04-01

Dyslipidemia has significantly contributed to the increase of death and morbidity rates related to cardiovascular diseases. Clinical nutrition service provided by dietitians has been reported to have a positive effect on relief of medical symptoms or reducing the further medical costs. However, there is a lack of researches to identify key competencies and job standard for clinical dietitians to care patients with dyslipidemia. Therefore, the purpose of this study was to analyze the job components of clinical dietitian and develop the standard for professional practice to provide effective nutrition management for dyslipidemia patients. The current status of clinical nutrition therapy for dyslipidemia patients in hospitals with 300 or more beds was studied. After duty tasks and task elements of nutrition care process for dyslipidemia clinical dietitians were developed by developing a curriculum (DACUM) analysis method. The developed job standards were pretested in order to evaluate job performance, difficulty, and job standards. As a result, the job standard included four jobs, 18 tasks, and 53 task elements, and specific job description includes 73 basic services and 26 recommended services. When clinical dietitians managing dyslipidemia patients performed their practice according to this job standard for 30 patients the job performance rate was 68.3%. Therefore, the job standards of clinical dietitians for clinical nutrition service for dyslipidemia patients proposed in this study can be effectively used by hospitals.

A systematic review of clinical assessment for undergraduate nursing students.

PubMed

Wu, Xi Vivien; Enskär, Karin; Lee, Cindy Ching Siang; Wang, Wenru

2015-02-01

Consolidated clinical practicum prepares pre-registration nursing students to function as beginning practitioners. The clinical competencies of final-year nursing students provide a key indication of professional standards of practice and patient safety. Thus, clinical assessment of nursing students is a crucial issue for educators and administrators. The aim of this systematic review was to explore the clinical competency assessment for undergraduate nursing students. PubMed, CINAHL, ScienceDirect, Web of Science, and EBSCO were systematically searched from January 2000 to December 2013. The systematic review was in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Published quantitative and qualitative studies that examined clinical assessment practices and tools used in clinical nursing education were retrieved. Quality assessment, data extraction, and analysis were completed on all included studies. This review screened 2073 titles, abstracts and full-text records, resulting in 33 included studies. Two reviewers assessed the quality of the included studies. Fourteen quantitative and qualitative studies were identified for this evaluation. The evidence was ordered into emergent themes; the overarching themes were current practices in clinical assessment, issues of learning and assessment, development of assessment tools, and reliability and validity of assessment tools. There is a need to develop a holistic clinical assessment tool with reasonable level of validity and reliability. Clinical assessment is a robust activity and requires collaboration between clinical partners and academia to enhance the clinical experiences of students, the professional development of preceptors, and the clinical credibility of academics. Copyright © 2014 Elsevier Ltd. All rights reserved.

The opportunities and obstacles in developing a vascular birthmark database for clinical and research use.

PubMed

Sharma, Vishal K; Fraulin, Frankie Og; Harrop, A Robertson; McPhalen, Donald F

2011-01-01

Databases are useful tools in clinical settings. The authors review the benefits and challenges associated with the development and implementation of an efficient electronic database for the multidisciplinary Vascular Birthmark Clinic at the Alberta Children's Hospital, Calgary, Alberta. The content and structure of the database were designed using the technical expertise of a data analyst from the Calgary Health Region. Relevant clinical and demographic data fields were included with the goal of documenting ongoing care of individual patients, and facilitating future epidemiological studies of this patient population. After completion of this database, 10 challenges encountered during development were retrospectively identified. Practical solutions for these challenges are presented. THE CHALLENGES IDENTIFIED DURING THE DATABASE DEVELOPMENT PROCESS INCLUDED: identification of relevant data fields; balancing simplicity and user-friendliness with complexity and comprehensive data storage; database expertise versus clinical expertise; software platform selection; linkage of data from the previous spreadsheet to a new data management system; ethics approval for the development of the database and its utilization for research studies; ensuring privacy and limited access to the database; integration of digital photographs into the database; adoption of the database by support staff in the clinic; and maintaining up-to-date entries in the database. There are several challenges involved in the development of a useful and efficient clinical database. Awareness of these potential obstacles, in advance, may simplify the development of clinical databases by others in various surgical settings.

A Leadership Education and Development Program for Clinical Nurses.

PubMed

Fitzpatrick, Joyce J; Modic, Mary Beth; Van Dyk, Jennifer; Hancock, K Kelly

2016-11-01

The Leadership Education and Development (LEAD) Program was designed to transform care at the bedside by empowering clinical nurses as leaders. The heart of LEAD was enhancing communication skills of clinical nurses with clinical colleagues and, most importantly, patients and families. Key concepts of leadership/management were included: personal awareness, personal leadership skills/abilities, leading change, leading others individually and in teams, enhancing the patient/provider experience, and the leadership role in outcomes management. A quantitative, longitudinal, survey design was used with 2 cohorts. The program consisted of six 4-hour sessions for 3 to 6 months. Leadership practices were measured before program implementation, at the end of the program, and 3 months after program completion. There were significant increases in leadership practices sustained 3 months after program completion. A range of other outcome measures was included. There is a need for additional leadership development programs for clinical nurses.

Advances in Probes and Methods for Clinical EPR Oximetry

PubMed Central

Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

2015-01-01

EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

Can Clinical Skills Be Taught Online? Comparing Skill Development between Online and F2F Students Using a Blinded Review

ERIC Educational Resources Information Center

Wilke, Dina J.; King, Erin; Ashmore, Margaret; Stanley, Craig

2016-01-01

This study compared the development of clinical assessment and intervention skills between students enrolled in a face-to-face (F2F) or an asynchronous online clinical social work class. All students from three semesters of F2F (n = 74) and online (n = 78) sections of an MSW clinical class taught by the same instructor were included. Two…

[Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

PubMed

Ying, Bin-Wu

2016-11-01

Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

Considerations in the development of circulating tumor cell technology for clinical use

PubMed Central

2012-01-01

This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI). PMID:22747748

Application of best practice approaches for designing decision support tools: The preparatory education about clinical trials (PRE-ACT) study

PubMed Central

Fleisher, Linda; Ruggieri, Dominique G.; Miller, Suzanne M.; Manne, Sharon; Albrecht, Terrance; Buzaglo, Joanne; Collins, Michael A.; Katz, Michael; Kinzy, Tyler G.; Liu, Tasnuva; Manning, Cheri; Charap, Ellen Specker; Millard, Jennifer; Miller, Dawn M.; Poole, David; Raivitch, Stephanie; Roach, Nancy; Ross, Eric A.; Meropol, Neal J.

2014-01-01

Objective This article describes the rigorous development process and initial feedback of the PRE-ACT (Preparatory Education About Clinical Trials) web-based- intervention designed to improve preparation for decision making in cancer clinical trials. Methods The multi-step process included stakeholder input, formative research, user testing and feedback. Diverse teams (researchers, advocates and developers) participated including content refinement, identification of actors, and development of video scripts. Patient feedback was provided in the final production period and through a vanguard group (N = 100) from the randomized trial. Results Patients/advocates confirmed barriers to cancer clinical trial participation, including lack of awareness and knowledge, fear of side effects, logistical concerns, and mistrust. Patients indicated they liked the tool’s user-friendly nature, the organized and comprehensive presentation of the subject matter, and the clarity of the videos. Conclusion The development process serves as an example of operationalizing best practice approaches and highlights the value of a multi-disciplinary team to develop a theory-based, sophisticated tool that patients found useful in their decision making process. Practice implications Best practice approaches can be addressed and are important to ensure evidence-based tools that are of value to patients and supports the usefulness of a process map in the development of e-health tools. PMID:24813474

Strengthening the Career Development of Clinical Translational Scientist Trainees: A Consensus Statement of the Clinical Translational Science Award (CTSA) Research Education and Career Development Committees

PubMed Central

Meyers, Frederick J.; Begg, Melissa D.; Fleming, Michael; Merchant, Carol

2012-01-01

Abstract  The challenges for scholars committed to successful careers in clinical and translational science are increasingly well recognized. The Education and Career Development (EdCD) of the national Clinical and Translational Science Award consortium gathered thought leaders to propose sustainable solutions and an agenda for future studies that would strengthen the infrastructure across the spectrum of pre‐ and postdoctoral, MD and PhD, scholars. Six consensus statements were prepared that include: (1) the requirement for career development of a qualitatively different investigator; (2) the implications of interdisciplinary science for career advancement including institutional promotion and tenure actions that were developed for discipline‐specific accomplishments; (3) the need for long‐term commitment of institutions to scholars; (4) discipline‐specific curricula are still required but curricula designed to promote team work and interdisciplinary training will promote innovation; (5) PhD trainees have many pathways to career satisfaction and success; and (6) a centralized infrastructure to enhance and reward mentoring is required. Several themes cut across all of the recommendations including team science, innovation, and sustained institutional commitment. Implied themes include an effective and diverse job force and the requirement for a well‐crafted public policy that supports continued investments in science education. Clin Trans Sci 2012; Volume #: 1–6 PMID:22507118

The impact of clinical nurse specialists on clinical pathways in the application of evidence-based practice.

PubMed

Gurzick, Martha; Kesten, Karen S

2010-01-01

The purpose of this article was to address the call for evidence-based practice through the development of clinical pathways and to assert the role of the clinical nurse specialist (CNS) as a champion in clinical pathway implementation. In the current health care system, providing quality of care while maintaining cost-effectiveness is an ever-growing battle that institutions face. The CNS's role is central to meeting these demands. An extensive literature review has been conducted to validate the use of clinical pathways as a means of improving patient outcomes. This literature also suggests that clinical pathways must be developed, implemented, and evaluated utilizing validated methods including the use of best practice standards. Execution of clinical pathways should include a clinical expert, who has the ability to look at the system as a whole and can facilitate learning and change by employing a multitude of competencies while maintaining a sphere of influence over patient and families, nurses, and the system. The CNS plays a pivotal role in influencing effective clinical pathway development, implementation, utilization, and ongoing evaluation to ensure improved patient outcomes and reduced costs. This article expands upon the call for evidence-based practice through the utilization of clinical pathways to improve patient outcomes and reduce costs and stresses the importance of the CNS as a primary figure for ensuring proper pathway development, implementation, and ongoing evaluation. Copyright 2010 Elsevier Inc. All rights reserved.

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

PubMed

Kontoghiorghe, Christina N; Kolnagou, Annita; Kontoghiorghes, George J

2015-11-23

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

Lessons learned from implementing service-oriented clinical decision support at four sites: A qualitative study.

PubMed

Wright, Adam; Sittig, Dean F; Ash, Joan S; Erickson, Jessica L; Hickman, Trang T; Paterno, Marilyn; Gebhardt, Eric; McMullen, Carmit; Tsurikova, Ruslana; Dixon, Brian E; Fraser, Greg; Simonaitis, Linas; Sonnenberg, Frank A; Middleton, Blackford

2015-11-01

To identify challenges, lessons learned and best practices for service-oriented clinical decision support, based on the results of the Clinical Decision Support Consortium, a multi-site study which developed, implemented and evaluated clinical decision support services in a diverse range of electronic health records. Ethnographic investigation using the rapid assessment process, a procedure for agile qualitative data collection and analysis, including clinical observation, system demonstrations and analysis and 91 interviews. We identified challenges and lessons learned in eight dimensions: (1) hardware and software computing infrastructure, (2) clinical content, (3) human-computer interface, (4) people, (5) workflow and communication, (6) internal organizational policies, procedures, environment and culture, (7) external rules, regulations, and pressures and (8) system measurement and monitoring. Key challenges included performance issues (particularly related to data retrieval), differences in terminologies used across sites, workflow variability and the need for a legal framework. Based on the challenges and lessons learned, we identified eight best practices for developers and implementers of service-oriented clinical decision support: (1) optimize performance, or make asynchronous calls, (2) be liberal in what you accept (particularly for terminology), (3) foster clinical transparency, (4) develop a legal framework, (5) support a flexible front-end, (6) dedicate human resources, (7) support peer-to-peer communication, (8) improve standards. The Clinical Decision Support Consortium successfully developed a clinical decision support service and implemented it in four different electronic health records and four diverse clinical sites; however, the process was arduous. The lessons identified by the Consortium may be useful for other developers and implementers of clinical decision support services. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Leveraging Big Data in Pediatric Development Programs: Proceedings From the 2016 American College of Clinical Pharmacology Annual Meeting Symposium.

PubMed

Mulugeta, Lily Yeruk; Yao, Lynne; Mould, Diane; Jacobs, Brian; Florian, Jeffrey; Smith, Brian; Sinha, Vikram; Barrett, Jeffrey S

2018-01-10

This article discusses the use of big data in pediatric drug development. The article covers key topics discussed at the ACCP annual meeting symposium in 2016 including the extent to which big data or real-world data can inform clinical trial design and substitute for efficacy and safety data typically obtained in clinical trials. The current states of use, opportunities, and challenges with the use of big data in future pediatric drug development are discussed. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Clinical pharmacology in Russia-historical development and current state.

PubMed

Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

2015-02-01

Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

Using Facebook to enhance commencing student confidence in clinical skill development: A phenomenological hermeneutic study.

PubMed

Watson, Bernadette; Cooke, Marie; Walker, Rachel

2016-01-01

The purpose of this study was to explore commencing nursing students' experience of Facebook as an adjunct to on-campus course delivery to determine its impact as a learning strategy for improving confidence in clinical skill development. Approaches supporting nursing students in the development of clinical skills have relied on 'real-life' clinical placements and simulated on-campus clinical laboratories. However students continue to report a lack of confidence in their clinical skills for practice. Social networking sites including Facebook are being used as a learning strategy to stimulate active and collaborative learning approaches. A hermeneutic phenomenological approach was used to provide an understanding of the experience of confidence in clinical skills development for nursing students. Data were collected through in-depth interviews with commencing students about their experience as learners using Facebook and their perceptions of the impact on their clinical skill development. Ten first-year student nurses at one university in south-east Queensland, Australia. Four themes emerged from the data including: 'We're all in this together'; 'I can do this'; 'This is about my future goals and success'; and, 'Real time is not fast enough!'. These themes provide new meaningful insights demonstrating students' sense of confidence in clinical skills was increased through engagement with a dedicated Facebook page. The findings of this study have relevance to academics in the design of learning strategies for clinical courses to further support student confidence and engagement through peer collaboration and active learning processes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Pediatric cardiovascular safety: challenges in drug and device development and clinical application.

PubMed

Bates, Katherine E; Vetter, Victoria L; Li, Jennifer S; Cummins, Susan; Aguel, Fernando; Almond, Christopher; Dubin, Anne M; Elia, Josephine; Finkle, John; Hausner, Elizabeth A; Joseph, Francesca; Karkowsky, Abraham M; Killeen, Matthew; Lemacks, Jodi; Mathis, Lisa; McMahon, Ann W; Pinnow, Ellen; Rodriguez, Ignacio; Stockbridge, Norman L; Stockwell, Margaret; Tassinari, Melissa; Krucoff, Mitchell W

2012-10-01

Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic. Copyright © 2012 Mosby, Inc. All rights reserved.

Reporting Items for Updated Clinical Guidelines: Checklist for the Reporting of Updated Guidelines (CheckUp)

PubMed Central

Vernooij, Robin W. M.; Alonso-Coello, Pablo; Brouwers, Melissa

2017-01-01

Background Scientific knowledge is in constant development. Consequently, regular review to assure the trustworthiness of clinical guidelines is required. However, there is still a lack of preferred reporting items of the updating process in updated clinical guidelines. The present article describes the development process of the Checklist for the Reporting of Updated Guidelines (CheckUp). Methods and Findings We developed an initial list of items based on an overview of research evidence on clinical guideline updating, the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument, and the advice of the CheckUp panel (n = 33 professionals). A multistep process was used to refine this list, including an assessment of ten existing updated clinical guidelines, interviews with key informants (response rate: 54.2%; 13/24), a three-round Delphi consensus survey with the CheckUp panel (33 participants), and an external review with clinical guideline methodologists (response rate: 90%; 53/59) and users (response rate: 55.6%; 10/18). CheckUp includes 16 items that address (1) the presentation of an updated guideline, (2) editorial independence, and (3) the methodology of the updating process. In this article, we present the methodology to develop CheckUp and include as a supplementary file an explanation and elaboration document. Conclusions CheckUp can be used to evaluate the completeness of reporting in updated guidelines and as a tool to inform guideline developers about reporting requirements. Editors may request its completion from guideline authors when submitting updated guidelines for publication. Adherence to CheckUp will likely enhance the comprehensiveness and transparency of clinical guideline updating for the benefit of patients and the public, health care professionals, and other relevant stakeholders. PMID:28072838

Clinical Supervision Skills: Managing the Clinical Environment. Health Occupations Clinical Teacher Education Series for Secondary and Post-Secondary Educators.

ERIC Educational Resources Information Center

Shea, Mary Lou; And Others

This learning module, which is part of a staff development program for health occupations clinical instructors, discusses the process of managing the physical clinical environment and students' experiences within the clinical environment. It includes learning activities dealing with various aspects of managing the physical environment and student…

New taxanes in development.

PubMed

Ferlini, Cristiano; Gallo, Daniela; Scambia, Giovanni

2008-03-01

Taxanes are presently widely employed for the medical treatment of cancer. However, despite the huge clinical success, these agents exhibit clinical problems related to poor drug solubility, toxicity and, in particular, drug resistance. To identify the critical points related to the process of development of novel taxanes. Publicly available data on the paclitaxel and docetaxel analogues, which have entered a clinical development phase in the last 2 years have been taken into consideration. The development involved novel formulations of paclitaxel and novel chemical entities. For each agent in each category the development phase is analysed and a synthetic comment for each category is included. Despite all the efforts, until now clinical success with the new development of taxanes has been limited. Moreover, the expected clinical introduction of epothilones could further restrict the space for development of novel taxanes. Despite these facts, some interesting concepts emerged during the process of development and could lead to successful drugs in the forthcoming years.

Competencies to enable learning-focused clinical supervision: a thematic analysis of the literature.

PubMed

Pront, Leeanne; Gillham, David; Schuwirth, Lambert W T

2016-04-01

Clinical supervision is essential for development of health professional students and widely recognised as a significant factor influencing student learning. Although considered important, delivery is often founded on personal experience or a series of predetermined steps that offer standardised behavioural approaches. Such a view may limit the capacity to promote individualised student learning in complex clinical environments. The objective of this review was to develop a comprehensive understanding of what is considered 'good' clinical supervision, within health student education. The literature provides many perspectives, so collation and interpretation were needed to aid development and understanding for all clinicians required to perform clinical supervision within their daily practice. A comprehensive thematic literature review was carried out, which included a variety of health disciplines and geographical environments. Literature addressing 'good' clinical supervision consists primarily of descriptive qualitative research comprising mostly small studies that repeated descriptions of student and supervisor opinions of 'good' supervision. Synthesis and thematic analysis of the literature resulted in four 'competency' domains perceived to inform delivery of learning-focused or 'good' clinical supervision. Domains understood to promote student learning are co-dependent and include 'to partner', 'to nurture', 'to engage' and 'to facilitate meaning'. Clinical supervision is a complex phenomenon and establishing a comprehensive understanding across health disciplines can influence the future health workforce. The learning-focused clinical supervision domains presented here provide an alternative perspective of clinical supervision of health students. This paper is the first step in establishing a more comprehensive understanding of learning-focused clinical supervision, which may lead to development of competencies for clinical supervision. © 2016 John Wiley & Sons Ltd.

Being a Clinical Educator

ERIC Educational Resources Information Center

Higgs, Joy; Mcallister, Lindy

2007-01-01

What is it like to be a clinical educator? How do clinical educators experience and describe their continuing journey of becoming a clinical educator? Within the model developed in this research, dimensions of being a clinical educator were identified. These dimensions include (a) having a sense of self (and the impact of bringing self into the…

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality

PubMed Central

von Niederhäusern, Belinda; Schandelmaier, Stefan; Mi Bonde, Marie; Brunner, Nicole; Hemkens, Lars G.; Rutquist, Marielle; Bhatnagar, Neera; Guyatt, Gordon H.; Pauli-Magnus, Christiane; Briel, Matthias

2017-01-01

Objective To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. Study design and setting We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Results Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Conclusion Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders’ individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research. PMID:28715491

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality.

PubMed

von Niederhäusern, Belinda; Schandelmaier, Stefan; Mi Bonde, Marie; Brunner, Nicole; Hemkens, Lars G; Rutquist, Marielle; Bhatnagar, Neera; Guyatt, Gordon H; Pauli-Magnus, Christiane; Briel, Matthias

2017-01-01

To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders' individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research.

Development and implementation of a psychotherapy tracking database in primary care.

PubMed

Craner, Julia R; Sawchuk, Craig N; Mack, John D; LeRoy, Michelle A

2017-06-01

Although there is a rapid increase in the integration of behavioral health services in primary care, few studies have evaluated the effectiveness of these services in real-world clinical settings, in part due to the difficulty of translating traditional mental health research designs to this setting. Accordingly, innovative approaches are needed to fit the unique challenges of conducting research in primary care. The development and implementation of one such approach is described in this article. A continuously populating database for psychotherapy services was implemented across 5 primary care clinics in a large health system to assess several levels of patient care, including service utilization, symptomatic outcomes, and session-by-session use of psychotherapy principles by providers. Each phase of implementation revealed challenges, including clinician time, dissemination to clinics with different resources, and fidelity of data collection strategy across providers, as well as benefits, including the generation of useful data to inform clinical care, program development, and empirical research. The feasible and sustainable implementation of data collection for routine clinical practice in primary care has the potential to fuel the evidence base around integrated care. The current project describes the development of an innovative approach that, with further empirical study and refinement, could enable health care professionals and systems to understand their population and clinical process in a way that addresses essential gaps in the integrated care literature. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

What should we teach the teachers? Identifying the learning priorities of clinical supervisors.

PubMed

Bearman, Margaret; Tai, Joanna; Kent, Fiona; Edouard, Vicki; Nestel, Debra; Molloy, Elizabeth

2018-03-01

Clinicians who teach are essential for the health workforce but require faculty development to improve their educational skills. Curricula for faculty development programs are often based on expert frameworks without consideration of the learning priorities as defined by clinical supervisors themselves. We sought to inform these curricula by highlighting clinical supervisors own requirements through answering the research question: what do clinical supervisors identify as relative strengths and areas for improvement in their teaching practice? This mixed methods study employed a modified version of the Maastricht Clinical Teaching Questionnaire (mMCTQ) which included free-text reflections. Descriptive statistics were calculated and content analysis was conducted on textual comments. 481 (49%) of 978 clinical supervisors submitted their mMCTQs and associated reflections for the research study. Clinical supervisors self-identified relatively strong capability with interpersonal skills or attributes and indicated least capability with assisting learners to explore strengths, weaknesses and learning goals. The qualitative category 'establishing relationships' was the most reported strength with 224 responses. The qualitative category 'feedback' was the most reported area for improvement, with 151 responses. Key areas for curricular focus include: improving feedback practices; stimulating reflective and agentic learning; and managing the logistics of a clinical education environment. Clinical supervisors' self-identified needs provide a foundation for designing engaging and relevant faculty development programs.

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

PubMed

Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

2017-06-15

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Exploring New Frontiers of Microsurgery: From Anatomy to Clinical Methods.

PubMed

Wang, Zeng Tao; Zheng, You Mao; Zhu, Lei; Hao, Li Wen; Zhang, Ya Bin; Chen, Chao; Xia, Li Feng; Liu, Lin Feng

2017-04-01

This article presents the authors' understanding and experience concerning anatomic studies and clinical methods in microsurgical hand reconstruction. The 4 parts of this article include anatomic study of the hand for developing new flaps; application of miniflaps from the hand, including clinical experience with 8 unique flaps in the hand; anatomic and clinical considerations concerning several flaps from other parts of the human body; And our experience with vascularized free toe joint transfer. Copyright © 2016 Elsevier Inc. All rights reserved.

Proceedings of the Annual National Clinic on Technical Education (12th, Spokane, Washington, March 26-28, 1975). Human Resource Development: Technical Education's Challenge.

ERIC Educational Resources Information Center

Rutledge, Gene; And Others

This report includes the presentations of the speakers appearing before the National Clinic on Technical Education. Topics cover human resource development; the impact of technical education on economic development (in Mississippi); economics of allied health education; manpower implications of environmental protection; manpower needs for…

Exploring the Clinical Utility of the Development and Well-Being Assessment (DAWBA) in the Detection of Hyperkinetic Disorders and Associated Diagnoses in Clinical Practice

ERIC Educational Resources Information Center

Foreman, David; Morton, Stephanie; Ford, Tamsin

2009-01-01

Background: The clinical diagnosis of ADHD is time-consuming and error-prone. Secondary care referral results in long waiting times, but primary care staff may not provide reliable diagnoses. The Development And Well-Being Assessment (DAWBA) is a standardised assessment for common child mental health problems, including attention…

Clinical Growth: An Evolutionary Concept Analysis.

PubMed

Barkimer, Jessica

2016-01-01

Clinical growth is an essential component of nursing education, although challenging to evaluate. Considering the paradigm shift toward constructivism and student-centered learning, clinical growth requires an examination within contemporary practices. A concept analysis of clinical growth in nursing education produced defining attributes, antecedents, and consequences. Attributes included higher-level thinking, socialization, skill development, self-reflection, self-investment, interpersonal communication, and linking theory to practice. Identification of critical attributes allows educators to adapt to student-centered learning in the clinical environment. These findings allow educators to determine significant research questions, develop situation-specific theories, and identify strategies to enhance student learning in the clinical environment.

[Development and application of hospital customer service center platform].

PubMed

Chen, Minya; Zheng, Konglin; Xia, Yong

2012-01-01

This paper introduces the construction and application of the platform of client service center in the general hospital and discusses how to provide patients with an entire service including service before clinic, on clinic and after clinic. It can also provide references for a new service mode for clinic service.

Clinical and Imaging Heterogeneity of Polymicrogyria: A Study of 328 Patients

ERIC Educational Resources Information Center

Leventer, Richard J.; Jansen, Anna; Pilz, Daniela T.; Stoodley, Neil; Marini, Carla; Dubeau, Francois; Malone, Jodie; Mitchell, L. Anne; Mandelstam, Simone; Scheffer, Ingrid E.; Berkovic, Samuel F.; Andermann, Frederick; Andermann, Eva; Guerrini, Renzo; Dobyns, William B.

2010-01-01

Polymicrogyria is one of the most common malformations of cortical development and is associated with a variety of clinical sequelae including epilepsy, intellectual disability, motor dysfunction and speech disturbance. It has heterogeneous clinical manifestations and imaging patterns, yet large cohort data defining the clinical and imaging…

Has molecular imaging delivered to drug development?

NASA Astrophysics Data System (ADS)

Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.

2017-10-01

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

Discovery and Development of Natural Product-derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach⊥†

PubMed Central

Lee, Kuo-Hsiung

2010-01-01

Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogs, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in Phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called “maturation inhibitors”. In addition, an etoposide analog, GL-331, progressed to anticancer Phase II clinical trials, and the curcumin analog JC-9 is in Phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trials candidates will also be discussed. PMID:20187635

The Future of Clinical Dentistry.

ERIC Educational Resources Information Center

Slavkin, Harold C.

1998-01-01

Discussion of the future of clinical dentistry looks at a variety of influences, including historical development factors; demographic trends; the role of the Human Genome Project in the development of scientific knowledge; a paradigm shift in approaches to oral infection and systemic disease; advancing technology; and reforms resulting from these…

A practical approach to competency assessment.

PubMed

Claflin, N

1997-01-01

Assessing clinical performance is difficult. Members of the Nursing Service Clinical Practice Committee at the Carl T. Hayden Veterans Affairs Medical Center in Phoenix developed a comprehensive program of competency assessment based on performance measures. This article describes the committee's process of developing and implementing the program and includes a blueprint for competency assessment and selected performance measures for all nursing staff who provide patient care. The approach to competency assessment includes performance measures specific to patients' ages.

Establishing Good Practices for Exposure–Response Analysis of Clinical Endpoints in Drug Development

PubMed Central

Overgaard, RV; Ingwersen, SH; Tornøe, CW

2015-01-01

This tutorial aims at promoting good practices for exposure–response (E-R) analyses of clinical endpoints in drug development. The focus is on practical aspects of E-R analyses to assist modeling scientists with a process of performing such analyses in a consistent manner across individuals and projects and tailored to typical clinical drug development decisions. This includes general considerations for planning, conducting, and visualizing E-R analyses, and how these are linked to key questions. PMID:26535157

Move to the head of the class: developing staff nurses as teachers.

PubMed

Donner, Carol L; Levonian, Catherine; Slutsky, Phyllis

2005-01-01

Nurses, while clinical experts in their specific fields, rarely have an opportunity to learn and practice teaching skills needed in an educator role. Clinical experts experience anxiety when asked to make the transition from a clinical environment to the teaching role. This article describes a 4-hour program developed to train nurses to become teachers. Adult learning principles, learning styles, and curriculum development were included to demonstrate the skills necessary to help nurses become proficient teachers.

How Can We Improve Outcomes for Patients and Families Under Palliative Care? Implementing Clinical Audit for Quality Improvement in Resource Limited Settings

PubMed Central

Selman, Lucy; Harding, Richard

2010-01-01

Palliative care in India has made enormous advances in providing better care for patients and families living with progressive disease, and many clinical services are well placed to begin quality improvement initiatives, including clinical audit. Clinical audit is recognized globally to be essential in all healthcare, as a way of monitoring and improving quality of care. However, it is not common in developing country settings, including India. Clinical audit is a cyclical activity involving: identification of areas of care in need of improvement, through data collection and analysis utilizing an appropriate questionnaire; setting measurable quality of care targets in specific areas; designing and implementing service improvement strategies; and then re-evaluating quality of care to assess progress towards meeting the targets. Outcome measurement is an important component of clinical audit that has additional advantages; for example, establishing an evidence base for the effectiveness of services. In resource limited contexts, outcome measurement in clinical audit is particularly important as it enables service development to be evidence-based and ensures resources are allocated effectively. Key success factors in conducting clinical audit are identified (shared ownership, training, managerial support, inclusion of all members of staff and a positive approach). The choice of outcome measurement tool is discussed, including the need for a culturally appropriate and validated measure which is brief and simple enough to incorporate into clinical practice and reflects the holistic nature of palliative care. Support for clinical audit is needed at a national level, and development and validation of an outcome measurement tool in the Indian context is a crucial next step. PMID:20859465

Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review.

PubMed

Wang, Yuchen; Newman, Maureen R; Benoit, Danielle S W

2018-06-01

Impaired fracture healing is a major clinical problem that can lead to patient disability, prolonged hospitalization, and significant financial burden. Although the majority of fractures heal using standard clinical practices, approximately 10% suffer from delayed unions or non-unions. A wide range of factors contribute to the risk for nonunions including internal factors, such as patient age, gender, and comorbidities, and external factors, such as the location and extent of injury. Current clinical approaches to treat nonunions include bone grafts and low-intensity pulsed ultrasound (LIPUS), which realizes clinical success only to select patients due to limitations including donor morbidities (grafts) and necessity of fracture reduction (LIPUS), respectively. To date, therapeutic approaches for bone regeneration rely heavily on protein-based growth factors such as INFUSE, an FDA-approved scaffold for delivery of bone morphogenetic protein 2 (BMP-2). Small molecule modulators and RNAi therapeutics are under development to circumvent challenges associated with traditional growth factors. While preclinical studies has shown promise, drug delivery has become a major hurdle stalling clinical translation. Therefore, this review overviews current therapies employed to stimulate fracture healing pre-clinically and clinically, including a focus on drug delivery systems for growth factors, parathyroid hormone (PTH), small molecules, and RNAi therapeutics, as well as recent advances and future promise of fracture-targeted drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Tissue fluid pressures - From basic research tools to clinical applications

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Akeson, Wayne H.; Mubarak, Scott J.; Owen, Charles A.; Gershuni, David H.

1989-01-01

This paper describes clinical applications of two basic research tools developed and refined in the past 20 years: the wick catheter (for measuring tissue fluid pressure) and the colloid osmometer (for measuring osmotic pressure). Applications of the osmometer include estimations of the reduced osmotic pressure of sickle-cell hemoglobin with deoxygenation, and of reduced swelling pressure of human nucleus pulposus with hydration or upon action of certain enzymes. Clinical uses of the wick-catheter technique include an improvement of diagnosis and treatment of acute and chronic compartment syndromes, the elucidation of the tissue pressure thresholds for neuromuscular dysfunction, and the development of a better tourniquet for orthopedics.

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials

PubMed Central

Bekelman, Justin E.; Deye, James A.; Vikram, Bhadrasain; Bentzen, Soren M.; Bruner, Deborah; Curran, Walter J.; Dignam, James; Efstathiou, Jason A.; FitzGerald, T. J.; Hurkmans, Coen; Ibbott, Geoffrey S.; Lee, J. Jack; Merchant, Timothy E.; Michalski, Jeff; Palta, Jatinder R.; Simon, Richard; Ten Haken, Randal K.; Timmerman, Robert; Tunis, Sean; Coleman, C. Norman; Purdy, James

2012-01-01

Background In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute (NCI) sponsored a two day workshop to examine the challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. Lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities like proton beam therapy, and the international harmonization of clinical trial QA. Results Four recommendations were made: 1) Develop a tiered (and more efficient) system for radiotherapy QA and tailor intensity of QA to clinical trial objectives. Tiers include (i) general credentialing, (ii) trial specific credentialing, and (iii) individual case review; 2) Establish a case QA repository; 3) Develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and 4) Explore the feasibility of consolidating clinical trial QA in the United States. Conclusion Radiotherapy QA may impact clinical trial accrual, cost, outcomes and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. PMID:22425219

Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference

PubMed Central

Lai, Wyman W.; Richmond, Marc; Li, Jennifer S.; Saul, J. Philip; Mital, Seema; Colan, Steven D.; Newburger, Jane W.; Sleeper, Lynn A.; McCrindle, Brain W.; Minich, L. LuAnn; Goldmuntz, Elizabeth; Marino, Bradley S.; Williams, Ismee A.; Pearson, Gail D.; Evans, Frank; Scott, Jane D.; Cohen, Meryl S.

2013-01-01

Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH–NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York–Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. PMID:21167335

The development of a clinical outcomes survey research application: Assessment Center.

PubMed

Gershon, Richard; Rothrock, Nan E; Hanrahan, Rachel T; Jansky, Liz J; Harniss, Mark; Riley, William

2010-06-01

The National Institutes of Health sponsored Patient-Reported Outcome Measurement Information System (PROMIS) aimed to create item banks and computerized adaptive tests (CATs) across multiple domains for individuals with a range of chronic diseases. Web-based software was created to enable a researcher to create study-specific Websites that could administer PROMIS CATs and other instruments to research participants or clinical samples. This paper outlines the process used to develop a user-friendly, free, Web-based resource (Assessment Center) for storage, retrieval, organization, sharing, and administration of patient-reported outcomes (PRO) instruments. Joint Application Design (JAD) sessions were conducted with representatives from numerous institutions in order to supply a general wish list of features. Use Cases were then written to ensure that end user expectations matched programmer specifications. Program development included daily programmer "scrum" sessions, weekly Usability Acceptability Testing (UAT) and continuous Quality Assurance (QA) activities pre- and post-release. Assessment Center includes features that promote instrument development including item histories, data management, and storage of statistical analysis results. This case study of software development highlights the collection and incorporation of user input throughout the development process. Potential future applications of Assessment Center in clinical research are discussed.

Experience with the Implementation of Clinical Pharmacy Services and Processes in a University Hospital in Belgium.

PubMed

Somers, Annemie; Claus, Barbara; Vandewoude, Koen; Petrovic, Mirko

2016-03-01

This article summarizes the experience with the development of clinical pharmacy services in the Ghent University Hospital in Belgium. Implementation of clinical pharmacy services in Belgian hospitals has not been evident because these activities were initially not structurally financed. The aim is to describe the strengths and weaknesses of the clinical pharmacy development process, and the milestones that enhanced the progress. Furthermore, the organisation of clinical pharmacy in the Ghent University Hospital is explained, including back- and front-office activities, seamless pharmaceutical care and medication safety improvement. Some working methods, procedures and tools are explained for different clinical pharmacy services. In particular, the clinical pharmacy projects for geriatric patients as well as the preparation of clinical pharmacy services for the accreditation process are explained. We also reflect on the organisation model and the future development of clinical pharmacy, taking into consideration facilitators and potential barriers.

The process and challenges of obtaining and sustaining clinical placements for nursing and allied health students.

PubMed

Taylor, Christine; Angel, Liz; Nyanga, Lucy; Dickson, Cathy

2017-10-01

To describe the process and challenges from a project that aimed to develop processes, source new placements and place students primarily in the discipline of nursing, but also occupational therapy, physiotherapy, podiatry, social work, and speech therapy. Clinical experience in health facilities is an essential element of health professional education, yet globally, there is a lack of clinical placements to meet demands. Educational providers are seeking placements in nontraditional facilities, yet little has been reported on the challenges in the process of procuring clinical placements. The project used a descriptive approach within a quality implementation framework. The project was guided by the quality implementation framework that included four critical steps: considerations of the host setting, structuring the implementation, supporting the implementation and improving future applications. A total of 115 new student placements were finalised across six health disciplines, including elderly care, nongovernment organisations and general practice. Sixty-two nursing students were placed in the new placements during the project. Challenges included communication, the time-consuming nature of the process and 'gatekeeping' blocks to obtaining placements. Recommendations included the importance of personal interaction in developing and maintaining relationships, and the need for clear communication processes and documentation. Potential areas for research are also given. There is great potential for growth in establishing new placements outside the traditional placement facilities for nursing and allied health and for expanding already existing nonhospital placements. Clinical professional experiences are essential to any nursing or allied health programme. There is an increasing demand for, and global lack of, clinical placements for nursing and allied health students. The results provide nursing and allied health educators and managers a framework for planning clinical placement procurement, and assisting in decision-making and developing strategies and processes for practice. © 2016 John Wiley & Sons Ltd.

An Analysis of Ambulatory Teaching Situations for Faculty Development.

ERIC Educational Resources Information Center

Simpson, Deborah E.; And Others

1990-01-01

A study identified variables perceived by clinical medical faculty (n=20) to influence the ease or difficulty of teaching in the ambulatory care setting. Characteristics affecting the teaching situation included teacher, student, and patient characteristics. Implications for faculty development on teaching in the clinical setting are discussed.…

A European multi-language initiative to make the general population aware of independent clinical research: the European Communication on Research Awareness Need project.

PubMed

Mosconi, Paola; Antes, Gerd; Barbareschi, Giorgio; Burls, Amanda; Demotes-Mainard, Jacques; Chalmers, Iain; Colombo, Cinzia; Garattini, Silvio; Gluud, Christian; Gyte, Gill; Mcllwain, Catherine; Penfold, Matt; Post, Nils; Satolli, Roberto; Valetto, Maria Rosa; West, Brian; Wolff, Stephanie

2016-01-12

The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence. The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project 2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six languages 5. Testing Treatments interactive in a dozen languages, including five official European Community languages 6. An interactive tutorial slide presentation testing viewers' knowledge about clinical trials Over a 2-year project, our multidisciplinary and multinational consortium was able to produce, and make freely available in many languages, new materials to promote public knowledge about the importance of independent and international clinical trials. Sustained funding for the ECRAN information platform could help to promote successful recruitment to independent clinical trials supported through the European Clinical Research Infrastructure Network.

Breaking barriers to novel analgesic drug development.

PubMed

Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P; Woolf, Clifford J

2017-08-01

Acute and chronic pain complaints, although common, are generally poorly served by existing therapies. This unmet clinical need reflects a failure to develop novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms, and the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.

Breaking barriers to novel analgesic drug development

PubMed Central

Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P.; Woolf, Clifford J.

2017-01-01

Acute and chronic pain complaints, while very common, are generally poorly served by existing therapies. The unmet clinical need reflects the failure in developing novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms coupled with the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities to develop new therapeutic strategies and revisit existing targets, including modulating ion channels, enzymes and GPCRs. PMID:28596533

Nurses’ Clinical Judgment Development: A Qualitative Research in Iran

PubMed Central

Seidi, Jamal; Alhani, Fatemeh; Salsali, Mahvash

2015-01-01

Background: Clinical judgment development is necessary because it leads to appropriate nursing diagnoses, clinical decision-making and health promotion. Objectives: In this study we explored the process of Iranian nurses’ development in clinical judgment. Patients and Methods: This qualitative study was conducted in 2013 at hospitals of Kurdistan University of Medical Sciences, located in the Sanandaj city of Iran. The data were collected based on semi-structured interviews and the study included 24 participants. Data analysis was carried out concurrently with data collection using the grounded theory method. Results: The study participants’ main concern was ‘being non-professional in clinical judgment’. In response to this concern, they were struggling for gaining professional autonomy, striving for integrating clinical judgment skills, scrambling to make effective educational interventions and striving for professional and inter professional collaboration in clinical judgment. The core category was ‘struggling for becoming professional in clinical judgment development’. When nurses were supported professionally, they were able to develop their professional clinical judgment. Conclusions: The findings of this study provided critical information about nurses’ professionalization in clinical judgment. Accordingly, the participants adopted different strategies to develop their clinical judgment ability. Integrating these strategies into nursing theory and clinical education can improve nurses’ clinical judgment ability. PMID:26473075

The Translational Science Benefits Model: A New Framework for Assessing the Health and Societal Benefits of Clinical and Translational Sciences

PubMed Central

Sarli, Cathy C.; Suiter, Amy M.; Carothers, Bobbi J.; Combs, Todd B.; Allen, Jae L.; Beers, Courtney E.; Evanoff, Bradley A.

2017-01-01

Abstract We report the development of the Translational Science Benefits Model (TSBM), a framework designed to support institutional assessment of clinical and translational research outcomes to measure clinical and community health impacts beyond bibliometric measures. The TSBM includes 30 specific and potentially measurable indicators that reflect benefits that accrue from clinical and translational science research such as products, system characteristics, or activities. Development of the TSBM was based on literature review, a modified Delphi method, and in‐house expert panel feedback. Three case studies illustrate the feasibility and face validity of the TSBM for identification of clinical and community health impacts that result from translational science activities. Future plans for the TSBM include further pilot testing and a resource library that will be freely available for evaluators, translational scientists, and academic institutions who wish to implement the TSBM framework in their own evaluation efforts. PMID:28887873

Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis.

PubMed

Velupillai, S; Mowery, D; South, B R; Kvist, M; Dalianis, H

2015-08-13

We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices.

FRAX(®) Bone Mineral Density Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

PubMed

Lewiecki, E Michael; Compston, Juliet E; Miller, Paul D; Adachi, Jonathan D; Adams, Judith E; Leslie, William D; Kanis, John A

2011-01-01

FRAX(®) is a fracture risk assessment algorithm developed by the World Health Organization in cooperation with other medical organizations and societies. Using easily available clinical information and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), when available, FRAX(®) is used to predict the 10-year probability of hip fracture and major osteoporotic fracture. These values may be included in country specific guidelines to aid clinicians in determining when fracture risk is sufficiently high that the patient is likely to benefit from pharmacological therapy to reduce that risk. Since the introduction of FRAX(®) into clinical practice, many practical clinical questions have arisen regarding its use. To address such questions, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundations (IOF) assigned task forces to review the best available medical evidence and make recommendations for optimal use of FRAX(®) in clinical practice. Questions were identified and divided into three general categories. A task force was assigned to investigating the medical evidence in each category and developing clinically useful recommendations. The BMD Task Force addressed issues that included the potential use of skeletal sites other than the femoral neck, the use of technologies other than DXA, and the deletion or addition of clinical data for FRAX(®) input. The evidence and recommendations were presented to a panel of experts at the ISCD-IOF FRAX(®) Position Development Conference, resulting in the development of ISCD-IOF Official Positions addressing FRAX(®)-related issues. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis

PubMed Central

Mowery, D.; South, B. R.; Kvist, M.; Dalianis, H.

2015-01-01

Summary Objectives We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. Methods We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Results Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. Conclusions There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices. PMID:26293867

Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

PubMed

Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

2016-11-01

This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial.

PubMed

Jabbour, Mona; Curran, Janet; Scott, Shannon D; Guttman, Astrid; Rotter, Thomas; Ducharme, Francine M; Lougheed, M Diane; McNaughton-Filion, M Louise; Newton, Amanda; Shafir, Mark; Paprica, Alison; Klassen, Terry; Taljaard, Monica; Grimshaw, Jeremy; Johnson, David W

2013-05-22

The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for 'point of care' management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma--the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis--the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process evaluation to assess the implementation strategy and an economic analysis to evaluate implementation costs and benefits. This study will contribute to the body of evidence supporting effective strategies for clinical pathway implementation, and ultimately reducing the research to practice gaps by operationalizing best evidence care recommendations through effective use of clinical pathways. ClinicalTrials.gov: NCT01815710.

Clinical validation of the Tempus xO assay

PubMed Central

Beaubier, Nike; Tell, Robert; Huether, Robert; Bontrager, Martin; Bush, Stephen; Parsons, Jerod; Shah, Kaanan; Baker, Tim; Selkov, Gene; Taxter, Tim; Thomas, Amber; Bettis, Sam; Khan, Aly; Lau, Denise; Lee, Christina; Barber, Matthew; Cieslik, Marcin; Frankenberger, Casey; Franzen, Amy; Weiner, Ali; Palmer, Gary; Lonigro, Robert; Robinson, Dan; Wu, Yi-Mi; Cao, Xuhong; Lefkofsky, Eric; Chinnaiyan, Arul; White, Kevin P.

2018-01-01

We have developed a clinically validated NGS assay that includes tumor, germline and RNA sequencing. We apply this assay to clinical specimens and cell lines, and we demonstrate a clinical sensitivity of 98.4% and positive predictive value of 100% for the clinically actionable variants measured by the assay. We also demonstrate highly accurate copy number measurements and gene rearrangement identification. PMID:29899824

An overview of clinical governance policies, practices and initiatives.

PubMed

Braithwaite, Jeffrey; Travaglia, Joanne F

2008-02-01

To map the emergence of, and define, clinical governance; to discuss current best practices, and to explore the implications of these for boards of directors and executives wishing to promote a clinical governance approach in their health services. Review and analysis of the published and grey literature on clinical governance from 1966 to 2006. Medline and CINAHL databases, key journals and websites were systematically searched. Central issues were identified in the literature as key to effective clinical governance. These include: ensuring that links are made between health services' clinical and corporate governance; the use of clinical governance to promote quality and safety through a focus on quality assurance and continuous improvement; the creation of clinical governance structures to improve safety and quality and manage risk and performance; the development of strategies to ensure the effective exchange of data, knowledge and expertise; and the sponsoring of a patient-centred approach to service delivery. A comprehensive approach to clinical governance necessarily includes the active participation of boards and executives in sponsoring and promoting clinical governance as a quality and safety strategy. Although this is still a relatively recent development, the signs are promising.

Knowledge Translation Tools are Emerging to Move Neck Pain Research into Practice.

PubMed

Macdermid, Joy C; Miller, Jordan; Gross, Anita R

2013-01-01

Development or synthesis of the best clinical research is in itself insufficient to change practice. Knowledge translation (KT) is an emerging field focused on moving knowledge into practice, which is a non-linear, dynamic process that involves knowledge synthesis, transfer, adoption, implementation, and sustained use. Successful implementation requires using KT strategies based on theory, evidence, and best practice, including tools and processes that engage knowledge developers and knowledge users. Tools can provide instrumental help in implementing evidence. A variety of theoretical frameworks underlie KT and provide guidance on how tools should be developed or implemented. A taxonomy that outlines different purposes for engaging in KT and target audiences can also be useful in developing or implementing tools. Theoretical frameworks that underlie KT typically take different perspectives on KT with differential focus on the characteristics of the knowledge, knowledge users, context/environment, or the cognitive and social processes that are involved in change. Knowledge users include consumers, clinicians, and policymakers. A variety of KT tools have supporting evidence, including: clinical practice guidelines, patient decision aids, and evidence summaries or toolkits. Exemplars are provided of two KT tools to implement best practice in management of neck pain-a clinician implementation guide (toolkit) and a patient decision aid. KT frameworks, taxonomies, clinical expertise, and evidence must be integrated to develop clinical tools that implement best evidence in the management of neck pain.

Patient-Reported Outcome and Observer-Reported Outcome Assessment in Rare Disease Clinical Trials: An ISPOR COA Emerging Good Practices Task Force Report.

PubMed

Benjamin, Katy; Vernon, Margaret K; Patrick, Donald L; Perfetto, Eleanor; Nestler-Parr, Sandra; Burke, Laurie

Rare diseases (RDs) affect a small number of people within a population. About 5000 to 8000 distinct RDs have been identified, with an estimated 6% to 8% of people worldwide suffering from an RD. Approximately 75% of RDs affect children. Frequently, these conditions are heterogeneous; many are progressive. Regulatory incentives have increased orphan drug designations and approvals. To develop emerging good practices for RD outcomes research addressing the challenges inherent in identifying, selecting, developing, adapting, and implementing patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments for use in RD clinical trials. This report outlines the challenges and potential solutions in determining clinical outcomes for RD trials. It follows the US Food and Drug Administration Roadmap to Patient-Focused Outcome Measurement in Clinical Trials. The Roadmap consists of three columns: 1) Understanding the Disease or Condition, 2) Conceptualizing Treatment Benefit, and 3) Selecting/Developing the Outcome Measure. Challenges in column 1 include factors such as incomplete natural history data and heterogeneity of disease presentation and patient experience. Solutions include using several information sources, for example, clinical experts and patient advocacy groups, to construct the condition's natural history and understand treatment patterns. Challenges in column 2 include understanding and measuring treatment benefit from the patient's perspective, especially given challenges in defining the context of use such as variations in age or disease severity/progression. Solutions include focusing on common symptoms across patient subgroups, identifying short-term outcomes, and using multiple types of COA instruments to measure the same constructs. Challenges in column 3 center around the small patient population and heterogeneity of the condition or study sample. Few disease-specific instruments for RDs exist. Strategies include adapting existing instruments developed for a similar condition or that contain symptoms of importance to the RD patient population, or using a generic instrument validated for the context of use. This report provides state-of-the-art solutions to patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments challenges in clinical trials of patients with RDs. These recommended solutions are both pragmatic and creative and posed with clear recognition of the global regulatory context used in RD clinical development programs. Copyright © 2017. Published by Elsevier Inc.

Geropsychology training in a specialist geropsychology doctoral program.

PubMed

Qualls, Sara Honn; Segal, Daniel L; Benight, Charles C; Kenny, Michael P

2005-01-01

The first PhD specialty program in Geropsychology that launched in fall, 2004 at CU-Colorado Springs is described. Consistent with a scientist-practitioner model, the curriculum sequence builds systematically from basic to complex knowledge and skills across the domains of scientific psychology, research methodology, general clinical, geropsychology science, and clinical geropsychology. Practicum experiences also build skills in core clinical competencies needed by geropsychologists, including assessment, psychotherapy, neuropsychological evaluations, caregiver consultation and counseling, health psychology, and outreach/prevention. Research mentoring prepares students with the skills needed to conduct independent research useful to the clinical practice of geropsychology. Challenges faced in the process of developing the program include the development of a training clinic, balancing specialty and generalized training, building a specialty culture while maintaining faculty integration, attracting faculty and students during a start-up phase, and defining an identity within the field. The mental health services center that was launched to meet training needs while addressing a services niche in the community contributes substantially to the essence of this program, and is described in some detail. Future opportunities and challenges include program funding, heavy demands of specialty training on top of generalist training, maintaining congruence between expectations of clinical and non-clinical faculty, providing interdisciplinary experience, and expansion of practicum opportunities.

Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

PubMed

Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

2010-04-20

The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that capacity development in clinical trials is best carried out in the context of preparation for specific trials. In this regard MCTA centres involved in the phase III malaria vaccine trial were, on average, more successful at consolidating the training and infrastructure support than those centres focussing only on drug trials.

Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

PubMed Central

2010-01-01

Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that capacity development in clinical trials is best carried out in the context of preparation for specific trials. In this regard MCTA centres involved in the phase III malaria vaccine trial were, on average, more successful at consolidating the training and infrastructure support than those centres focussing only on drug trials. PMID:20406478

EUFEMED London Conference 2017: Exploratory Medicines Development: Innovation and Risk Management.

PubMed

Van Bortel, Luc; Sourgens, Hildegard; Breithaupt-Grögler, Kerstin; Caplain, Henri; Donazzolo, Yves; Klingmann, Ingrid; Hammond, Michael; Hardman, Timothy C; Stringer, Steffan; de Hoon, Jan

2017-01-01

The first formal conference of the EUropean Federation for Exploratory MEdicines Development (EUFEMED) held in London was the result of a collaborative effort of its founding associations: the Association for Applied Human Pharmacology (AGAH; Germany), the Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI; UK), the Belgian Association of Phase-I Units (BAPU; Belgium), and Club Phase-I (France). The conference focused on innovation and risk management in early clinical drug development. Among other innovations, immunotherapy in oncology and inflammatory diseases were discussed as well as the importance of adaptive trial designs in early clinical drug development. Consideration was given to assessing and mitigating risk in early clinical drug development, and included a preconference workshop. Different measures to minimize risks in healthy volunteers and patients in first-in-human trials were discussed in addition to the importance of non-clinical data, the need for reliable biomarkers, improved communication on adverse events (AEs) and well-trained study sites with ready access to intensive care units and clinical specialists. The need for a European-wide system for prevention of over-volunteering was also discussed. The conference provided opportunity to discuss these developments and concerns and the changing regulatory environment with stakeholders from academia, industry, and regulatory agencies including the European Medicines Agency (EMA). Presentations given by invited speakers are published on http://www.eufemed.eu/london-conference-2017/.

An interview study of how clinical teachers develop skills to attend to different level learners.

PubMed

Chen, H Carrie; Fogh, Shannon; Kobashi, Brent; Teherani, Arianne; Ten Cate, Olle; O'Sullivan, Patricia

2016-06-01

One clinical teaching challenge is the engagement of learners at different levels. Faculty development offerings mostly address general strategies applicable to all learners. This study examined how clinical faculty members develop the skills to work with different level learners. We conducted semi-structured interviews with medical school faculty members identified as excellent clinical teachers teaching multiple levels of learners. They discussed how they developed their approach to teaching different level learners and how their teaching evolved over time. We performed thematic analysis of the interview transcripts using open and axial coding. We interviewed 19 faculty members and identified three themes related to development of teaching practices: teacher agency and work-based learning of teaching strategies, developmental trajectory of clinical teachers, and interplay between clinical confidence and teaching skills. Faculty members were proactive in using on-the-job experiences to develop their teaching practices. Their teaching practices followed a developmental trajectory towards learner centeredness, and this evolution was associated with the development of clinical skills and confidence. Learning skills to teach multi-level learners requires workplace learning. Faculty development should include workplace learning opportunities and use a developmental approach that accounts for the trajectory of teaching as well as clinical skills attainment.

A Systematic Review of Smartphone Applications for Plastic Surgery Providers: Target Audience, Uses, and Cost.

PubMed

Reusche, Ryan; Buchanan, Patrick J; Kozlow, Jeffrey H; Vercler, Christian J

2016-01-01

The growth and acceptance of smartphones among clinicians has been remarkable over the last decade. Over 87% of doctors use a smartphone or tablet capable of running third-party software known as applications (apps). In the field of plastic surgery, apps have been designed for personal practice development, education, clinical tools and guidelines, and entertainment. This study reviews the literature on apps related to plastic surgery and determines the number and types of apps available. A systematic review of the literature was performed to find articles written about plastic surgery applications. Queries were run in the Apple iPhone iOS App store and Google Play using the term "plastic surgery." Apps were reviewed for ratings, downloads, and cost. In addition, apps were categorized based on purpose. Categories include practice development, media/literature, clinical tool and guideline apps, or recreation. The literature search yielded 8 articles for review, 2 articles focused on categorizing apps and 6 articles focused on describing useful apps. Searching Apple's iTunes (iOS) store identified 273 and Google Play identified 250 apps related to plastic surgery; since 2013, a 62%, and 580% increase, respectively. The iOS store included practice development (46%), recreation (26%), media/literature (14%), and clinical tool and guideline (11%). Google Play store included recreation apps (44%), practice development (24%), clinical tools and guidelines (11%), and media and literature (9%). Apps related to the field of plastic surgery are increasing in prevalence. The content of these apps are variable, and the majority are intended for marketing and development of private practices. Apps linking to literature, texts, study materials, and clinical tools and guidelines are developed for both practicing plastic surgeons and surgical trainees. Finding "useful" apps takes time because searches are often complicated by a variety of apps.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

PubMed

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

[The informed consent in international clinical trials including developing countries].

PubMed

Montenegro Surís, Alexander; Monreal Agüero, Magda Elaine

2008-01-01

The informed consent procedure has been one of the most important controversies of ethical debates about clinical trials in developing countries. In this essay we present our recommendations about important aspects to consider in the informed consent procedure for clinical trials in developing countries. We performed a full publications review identified by MEDLINE using these terms combinations: informed consent, developing countries, less developed countries and clinical trials. To protect volunteers in less developed countries should be valuated the importance of the community in the informed consent proceeding. The signing and dating of the informed consent form is not always the best procedure to document the informed consent. The informed consent form should be written by local translators. Alternative medias of communications could be needed for communicatios of the information to volunteers. Comparing with developed countries the informed consent proceeding in clinical trials in developing countries frequently require additional efforts. The developing of pragmatic researches is needed to implement informed consent proceedings assuring subjects voluntarily in each developing country. The main aspects to define in each clinical trial for each country are the influence of the community, the effective communication of the information, the documentation of the informed consent and local authority's control.

Gene therapy for heart disease: molecular targets, vectors and modes of delivery to myocardium.

PubMed

Scimia, Maria Cecilia; Cannavo, Alessandro; Koch, Walter J

2013-08-01

Despite the numerous hurdles that gene therapy has encountered along the way, clinical trials over the last few years are showing promising results in many fields of medicine, including cardiology, where many targets are moving toward clinical development. In this review, the authors discuss the current state of the art in terms of clinical and preclinical development. They also examine vector technology and available vector-delivery strategies.

Acromegaly: an endocrine society clinical practice guideline.

PubMed

Katznelson, Laurence; Laws, Edward R; Melmed, Shlomo; Molitch, Mark E; Murad, Mohammad Hassan; Utz, Andrea; Wass, John A H

2014-11-01

The aim was to formulate clinical practice guidelines for acromegaly. The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.

Automated information systems provide health information management support to veterans' healthcare.

PubMed

Lloyd, S S

1992-06-01

The Veterans Health Administration has implemented a comprehsnsive DHCP which supports the VA healthcare system at both local and national levels. Numerous clinical and management modules have been developed; an overview was given of selected applications impacting health information managers. Continuing development includes an automated clinical record and expanded electronic data exchange.

Developing core outcome sets for clinical trials: issues to consider

PubMed Central

2012-01-01

The selection of appropriate outcomes or domains is crucial when designing clinical trials in order to compare directly the effects of different interventions in ways that minimize bias. If the findings are to influence policy and practice then the chosen outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set, which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for general guidance on the development of core outcome sets. Key issues to consider in the development of a core outcome set include its scope, the stakeholder groups to involve, choice of consensus method and the achievement of a consensus. PMID:22867278

Development and implementation of sepsis alert systems

PubMed Central

Harrison, Andrew M.; Gajic, Ognjen; Pickering, Brian W.; Herasevich, Vitaly

2016-01-01

Synopsis/Summary Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Important barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload & alert fatigue, due to suboptimal alert performance. Outside the ICU, additional barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Currently available evidence does not support routine use of sepsis alert systems in clinical practice. However, continuous improvement in both the afferent (data availability and accuracy of detection algorithms) and efferent (evidence-based decision support and smoother integration into clinical workflow) limbs of sepsis alert systems will help translate theoretical advantages into measurable patient benefit. PMID:27229639

From Cheerleader to Coach: The Developmental Progression of Bedside Teachers in Giving Feedback to Early Learners.

PubMed

Wenrich, Marjorie D; Jackson, Molly Blackley; Maestas, Ramoncita R; Wolfhagen, Ineke H A P; Scherpbier, Albert J J

2015-11-01

Medical students learn clinical skills at the bedside from teaching clinicians, who often learn to teach by teaching. Little is known about the process of becoming an effective clinical teacher. Understanding how teaching skills and approaches change with experience may help tailor faculty development for new teachers. Focusing on giving feedback to early learners, the authors asked: What is the developmental progression of clinician-teachers as they learn to give clinical skills feedback to medical students? This qualitative study included longitudinal interviews with clinician-teachers over five years in a new clinical skills teaching program for preclinical medical students. Techniques derived from grounded theory were used for initial analyses. The current study focused on one theme identified in initial analyses: giving feedback to students. Transcript passages were organized by interview year, coded, and discussed in year clusters; thematic codes were compared and emergent codes developed. Themes related to giving feedback demonstrated a dyadic structure: characteristic of less experienced teachers versus characteristic of experienced teachers. Seven dominant dyadic themes emerged, including teacher as cheerleader versus coach, concern about student fragility versus understanding resilience, and focus on creating a safe environment versus challenging students within a safe environment. With consistent teaching, clinical teachers demonstrated progress in giving feedback to students in multiple areas, including understanding students' developmental trajectory and needs, developing tools and strategies, and adopting a dynamic, challenging, inclusive team approach. Ongoing teaching opportunities with targeted faculty development may help improve clinician-teachers' feedback skills and approaches.

Clinical governance and external audit.

PubMed

Glazebrook, S G; Buchanan, J G

2001-01-01

This paper describes a model of clinical governance that was developed at South Auckland Health during the period 1995 to 2000. Clinical quality and safety are core objectives. A multidisciplinary Clinical Board is responsible for the development and publicising of sound clinical policies together with monitoring the effects of their implementation on quality and safety. The Clinical Board has several committees, including an organization-wide Continuous Quality Improvement Committee to enhance the explicit nature of the quality system in terms of structure, staff awareness and involvement, and to develop the internal audit system. The second stream stems from the Chief Medical Officer and clinical directors in a clinical management sense. The Audit Committee of the Board of Directors covers both clinical and financial audit. The reporting lines back to that committee are described and the role of the external auditor of clinical standards is explained. The aim has been to create a supportive culture where quality initiatives and innovation can flourish, and where the emphasis is not on censure but improvement.

The Resource Team: an innovative service delivery support model for mental health services.

PubMed

O'Sullivan, Julie; Powell, Jacinta; Gibbon, Peter; Emmerson, Brett

2009-04-01

This paper outlines the development of the Resource Team, an innovative service delivery model supporting clinical services at the Inner North Brisbane Mental Health Service, Royal Brisbane and Women's Hospital Health Service District. The team aims to provide a base for specialist mental health support staff, improve knowledge management and support the development of meaningful community partnerships. Development of the team included a literature review and consultation with internal and external stakeholders. From this, the objectives, roles and functions of the team were clarified and disseminated to stakeholders. The team currently encompasses 12 positions and has initiated a number of programs and service developments. These include improved IT management of clinical resources and the development of partnerships with the community and non-government sectors. The Resource Team effectively coordinates specialist clinical support positions, addresses knowledge management issues and facilitates meaningful engagement with the community and non-government sectors. The model could easily be applied in other mental health and general health services.

The basics of preclinical drug development for neurodegenerative disease indications.

PubMed

Steinmetz, Karen L; Spack, Edward G

2009-06-12

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and services to assist applicants in preparing the preclinical programs and documentation for their drugs. Increasingly, private foundations are also funding preclinical work. Close interaction with the FDA, including a meeting to prepare for submission of an Investigational New Drug application, is critical to ensure that the preclinical development package properly supports the planned phase I clinical trial.

The basics of preclinical drug development for neurodegenerative disease indications

PubMed Central

Steinmetz, Karen L; Spack, Edward G

2009-01-01

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and services to assist applicants in preparing the preclinical programs and documentation for their drugs. Increasingly, private foundations are also funding preclinical work. Close interaction with the FDA, including a meeting to prepare for submission of an Investigational New Drug application, is critical to ensure that the preclinical development package properly supports the planned phase I clinical trial. PMID:19534731

Faculty development: a 'field of dreams'?

PubMed

Steinert, Yvonne; McLeod, Peter J; Boillat, Miriam; Meterissian, Sarkis; Elizov, Michelle; Macdonald, Mary Ellen

2009-01-01

Participants in faculty development workshops often comment that 'those who need faculty development the most attend the least'. The goals of this study were to explore the reasons why some clinical teachers do not participate in centralised faculty development activities and to learn how we can make faculty development programmes more relevant to teachers' needs. In 2006, we conducted focus groups with 16 clinical teachers, who had not participated in faculty development activities, to ascertain their perceptions of faculty development, reasons for non-participation and perceived barriers to involvement. Content analysis and team consensus guided the data interpretation. Focus group participants were aware of faculty development offerings and valued the goals of these activities. Important reasons for non-participation emerged: clinical reality, which included volume of work and lack of (protected) time; logistical issues, such as timing and the central location of organised activities; a perceived lack of financial reward and recognition for teaching, and a perceived lack of direction from, and connection to, the university. Clinical reality and logistical issues appeared to be greater deterrents to participation than faculty development goals, content or strategies. Moreover, when asked to discuss faculty development, teachers referred to their development as faculty members in the broadest sense, which included personal and career development. They also expressed the desire for clear guidance from the university, financial rewards and recognition for teaching, and a sense of 'belonging'. Faculty development programmes should try to address these organisational issues as well as teachers' personal and professional needs.

Paving the critical path: how can clinical pharmacology help achieve the vision?

PubMed

Lesko, L J

2007-02-01

It has been almost 3 years since the launch of the FDA critical path initiative following the publication of the paper "Innovation or Stagnation: Challenges and Opportunities on the Critical Path of New Medical Product Development." The initiative was intended to create an urgency with the drug development enterprise to address the so-called "productivity problem" in modern drug development. Clinical pharmacologists are strategically aligned with solutions designed to reduce late phase clinical trial failures to show adequate efficacy and/or safety. This article reviews some of the ways that clinical pharmacologists can lead and implement change in the drug development process. It includes a discussion of model-based, semi-mechanistic drug development, drug/disease models that facilitate informed clinical trial designs and optimal dosing, the qualification process and criteria for new biomarkers and surrogate endpoints, approaches to streamlining clinical trials and new types of interaction between industry and FDA such as the end-of-phase 2A and voluntary genomic data submission meetings respectively.

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials-Report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bekelman, Justin E., E-mail: bekelman@uphs.upenn.edu; Deye, James A.; Vikram, Bhadrasain

2012-07-01

Purpose: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods and Materials: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such asmore » proton beam therapy, and the international harmonization of clinical trial QA. Results: Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Conclusion: Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based.« less

Redesigning radiotherapy quality assurance: opportunities to develop an efficient, evidence-based system to support clinical trials--report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance.

PubMed

Bekelman, Justin E; Deye, James A; Vikram, Bhadrasain; Bentzen, Soren M; Bruner, Deborah; Curran, Walter J; Dignam, James; Efstathiou, Jason A; FitzGerald, T J; Hurkmans, Coen; Ibbott, Geoffrey S; Lee, J Jack; Merchant, Thomas E; Michalski, Jeff; Palta, Jatinder R; Simon, Richard; Ten Haken, Randal K; Timmerman, Robert; Tunis, Sean; Coleman, C Norman; Purdy, James

2012-07-01

In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA. Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical protein science developments for patient monitoring in hospital central laboratories.

PubMed

Malm, Johan; Marko-Varga, György

2016-12-01

Patient care relies heavily on standardized tests performed in hospital laboratories, typically including clinical chemistry, pathology and microbiology. With the introduction of personalized medicine tremendous efforts have been made to identify new biomarkers of disease with various omics technologies, often including mass spectrometry. In order to validate new biomarkers and perform clinical studies high quality biobank samples are of key importance. In this editorial different aspects of mass spectrometry in future personalized medicine are discussed.

Rehabilitation and the Veterans' Administration

NASA Technical Reports Server (NTRS)

Meister, F.

1974-01-01

The Veteran's Administration health care system provides prosthetic and sensory aids for the rehabilitation of neurologically handicapped veterans. Research and development centers include prosthetic clinic teams, orthopedic shops, restoration clinics, bioengineering services, orthotics, etc.

Dry Macular Degeneration

MedlinePlus

... developing macular degeneration. Include fish in your diet. Omega-3 fatty acids, which are found in fish, may ... macular degeneration. Nuts, such as walnuts, also contain omega-3 fatty acids. By Mayo Clinic Staff . Mayo Clinic ...

Progress in evidence-based medicine: a quarter century on.

PubMed

Djulbegovic, Benjamin; Guyatt, Gordon H

2017-07-22

In response to limitations in the understanding and use of published evidence, evidence-based medicine (EBM) began as a movement in the early 1990s. EBM's initial focus was on educating clinicians in the understanding and use of published literature to optimise clinical care, including the science of systematic reviews. EBM progressed to recognise limitations of evidence alone, and has increasingly stressed the need to combine critical appraisal of the evidence with patient's values and preferences through shared decision making. In another progress, EBM incorporated and further developed the science of producing trustworthy clinical practice guidelines pioneered by investigators in the 1980s. EBM's enduring contributions to clinical medicine include placing the practice of medicine on a solid scientific basis, the development of more sophisticated hierarchies of evidence, the recognition of the crucial role of patient values and preferences in clinical decision making, and the development of the methodology for generating trustworthy recommendations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Internet and cardiovascular research: the present and its future potentials and limits.

PubMed

2002-03-01

The Internet and the World Wide Web have been proposed as tools to improve medical and cardiovascular research. These new technologies have been mainly applied to large-scale clinical trials, with the development of clinical-trial websites. They include tools for the management of some aspects of clinical trials, such as the dissemination of information on trial progress; randomisation and the monitoring processes; the distribution and accountability of study drugs; and remote data-entry. Several clinical-trial websites have been developed in the cardiovascular field over the last few years, but few have been designed to conduct trials fully online. Advantages of such systems include greater interaction between the coordinating centre and investigators, availability of a clean database in a short time, and cost reduction. Website developers need to take care of security issues and to use security tools (data encryption, firewalls, passwords and electronic signatures) in order to prevent unauthorised users from accessing the system and patient data.

Improving Clinical Practices for Children with Language and Learning Disorders

ERIC Educational Resources Information Center

Kamhi, Alan G.

2014-01-01

Purpose: This lead article of the Clinical Forum addresses some of the gaps that exist between clinical practice and current knowledge about instructional factors that influence learning and language development. Method: Topics reviewed and discussed include principles of learning, generalization, treatment intensity, processing interventions,…

[Microdose clinical trial--impact of PET molecular imaging].

PubMed

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

Dashboard systems: implementing pharmacometrics from bench to bedside.

PubMed

Mould, Diane R; Upton, Richard N; Wojciechowski, Jessica

2014-09-01

In recent years, there has been increasing interest in the development of medical decision-support tools, including dashboard systems. Dashboard systems are software packages that integrate information and calculations about therapeutics from multiple components into a single interface for use in the clinical environment. Given the high cost of medical care, and the increasing need to demonstrate positive clinical outcomes for reimbursement, dashboard systems may become an important tool for improving patient outcome, improving clinical efficiency and containing healthcare costs. Similarly the costs associated with drug development are also rising. The use of model-based drug development (MBDD) has been proposed as a tool to streamline this process, facilitating the selection of appropriate doses and making informed go/no-go decisions. However, complete implementation of MBDD has not always been successful owing to a variety of factors, including the resources required to provide timely modeling and simulation updates. The application of dashboard systems in drug development reduces the resource requirement and may expedite updating models as new data are collected, allowing modeling results to be available in a timely fashion. In this paper, we present some background information on dashboard systems and propose the use of these systems both in the clinic and during drug development.

Effectiveness of a Simulated Clinical Examination in the Assessment of the Clinical Competencies of Entry-Level Trainees in a Family Medicine Residency Programme

ERIC Educational Resources Information Center

Curran, Vernon R.; Butler, Roger; Duke, Pauline; Eaton, William H.; Moffatt, Scott M.; Sherman, Greg P.; Pottle, Madge

2012-01-01

Clinical competence is a multidimensional concept and encompasses a variety of skills including procedural, problem-solving and clinical judgement. The initial stages of postgraduate medical training are believed to be a particularly important time for the development of clinical skill competencies. This study reports on an evaluation of a…

Clinical neuropsychology in South Korea.

PubMed

Kim, Myung-Sun; Chey, Jeanyung

2016-11-01

Clinical neuropsychology in South Korea, albeit its relatively short history, has advanced dramatically. We review a brief history and current status of clinical neuropsychology in South Korea. The history, the educational pathway, the training pathway, the certification process, and careers in clinical neuropsychology in South Korea are reviewed. We have reviewed the neuropsychological services, including assessment and treatment, research on neurological and psychiatric populations, and neuropsychology education and the requirements related to education, training, and board examinations of those providing neuropsychological services in South Korea. We also describe how the Korean Society for Neuropsychology Research, the first and only meeting for neuropsychologists in the country established in 1999, has played a major role in how clinical neuropsychology is practiced and developed as a professional field in South Korea. Clinical neuropsychology in South Korea has achieved major progress over just a quarter of a century, and its future is promising in light of the increasing demand for neuropsychological services and advances in neuroscience in the country. Challenges that the community of clinical neuropsychologists are currently facing in South Korea, including formalizing neuropsychological curriculum and training programs and developing advanced credentialing procedures, are discussed.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

PubMed

Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

2015-05-01

The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

High-Resolution Methods for Diagnosing Cartilage Damage In Vivo

PubMed Central

Novakofski, Kira D.; Pownder, Sarah L.; Koff, Matthew F.; Williams, Rebecca M.; Potter, Hollis G.; Fortier, Lisa A.

2016-01-01

Advances in current clinical modalities, including magnetic resonance imaging and computed tomography, allow for earlier diagnoses of cartilage damage that could mitigate progression to osteoarthritis. However, current imaging modalities do not detect submicrometer damage. Developments in in vivo or arthroscopic techniques, including optical coherence tomography, ultrasonography, bioelectricity including streaming potential measurement, noninvasive electroarthrography, and multiphoton microscopy can detect damage at an earlier time point, but they are limited by a lack of penetration and the ability to assess an entire joint. This article reviews current advancements in clinical and developing modalities that can aid in the early diagnosis of cartilage injury and facilitate studies of interventional therapeutics. PMID:26958316

Information management to enable personalized medicine: stakeholder roles in building clinical decision support.

PubMed

Downing, Gregory J; Boyle, Scott N; Brinner, Kristin M; Osheroff, Jerome A

2009-10-08

Advances in technology and the scientific understanding of disease processes are presenting new opportunities to improve health through individualized approaches to patient management referred to as personalized medicine. Future health care strategies that deploy genomic technologies and molecular therapies will bring opportunities to prevent, predict, and pre-empt disease processes but will be dependent on knowledge management capabilities for health care providers that are not currently available. A key cornerstone to the potential application of this knowledge will be effective use of electronic health records. In particular, appropriate clinical use of genomic test results and molecularly-targeted therapies present important challenges in patient management that can be effectively addressed using electronic clinical decision support technologies. Approaches to shaping future health information needs for personalized medicine were undertaken by a work group of the American Health Information Community. A needs assessment for clinical decision support in electronic health record systems to support personalized medical practices was conducted to guide health future development activities. Further, a suggested action plan was developed for government, researchers and research institutions, developers of electronic information tools (including clinical guidelines, and quality measures), and standards development organizations to meet the needs for personalized approaches to medical practice. In this article, we focus these activities on stakeholder organizations as an operational framework to help identify and coordinate needs and opportunities for clinical decision support tools to enable personalized medicine. This perspective addresses conceptual approaches that can be undertaken to develop and apply clinical decision support in electronic health record systems to achieve personalized medical care. In addition, to represent meaningful benefits to personalized decision-making, a comparison of current and future applications of clinical decision support to enable individualized medical treatment plans is presented. If clinical decision support tools are to impact outcomes in a clear and positive manner, their development and deployment must therefore consider the needs of the providers, including specific practice needs, information workflow, and practice environment.

Information management to enable personalized medicine: stakeholder roles in building clinical decision support

PubMed Central

2009-01-01

Background Advances in technology and the scientific understanding of disease processes are presenting new opportunities to improve health through individualized approaches to patient management referred to as personalized medicine. Future health care strategies that deploy genomic technologies and molecular therapies will bring opportunities to prevent, predict, and pre-empt disease processes but will be dependent on knowledge management capabilities for health care providers that are not currently available. A key cornerstone to the potential application of this knowledge will be effective use of electronic health records. In particular, appropriate clinical use of genomic test results and molecularly-targeted therapies present important challenges in patient management that can be effectively addressed using electronic clinical decision support technologies. Discussion Approaches to shaping future health information needs for personalized medicine were undertaken by a work group of the American Health Information Community. A needs assessment for clinical decision support in electronic health record systems to support personalized medical practices was conducted to guide health future development activities. Further, a suggested action plan was developed for government, researchers and research institutions, developers of electronic information tools (including clinical guidelines, and quality measures), and standards development organizations to meet the needs for personalized approaches to medical practice. In this article, we focus these activities on stakeholder organizations as an operational framework to help identify and coordinate needs and opportunities for clinical decision support tools to enable personalized medicine. Summary This perspective addresses conceptual approaches that can be undertaken to develop and apply clinical decision support in electronic health record systems to achieve personalized medical care. In addition, to represent meaningful benefits to personalized decision-making, a comparison of current and future applications of clinical decision support to enable individualized medical treatment plans is presented. If clinical decision support tools are to impact outcomes in a clear and positive manner, their development and deployment must therefore consider the needs of the providers, including specific practice needs, information workflow, and practice environment. PMID:19814826

Education strategies to foster health professional students' clinical reasoning skills.

PubMed

Rochmawati, Erna; Wiechula, Rick

2010-06-01

Clinical reasoning is an important skill for health professionals that should be developed to achieve high levels of expertise. Several education strategies have been suggested for implementation by health professional educators to foster their students' clinical reasoning skills. The strategies have included the following: problem-based learning, the integrative curriculum, reflection, and concept mapping. This review assesses which is the most effective education strategy for developing the clinical reasoning skills of health professional students. Four publications, from a total of 692 identified records, were included. Overall, this review was not able to make a final conclusion to answer the question. Therefore, there is a need to conduct more studies with larger samples and to undertake research that evaluates the following aspects: more alternate education interventions, variations in the delivery of education interventions, and the cost-effectiveness of implementing education strategies.

The development of a clinical outcomes survey research application: Assessment CenterSM

PubMed Central

Rothrock, Nan E.; Hanrahan, Rachel T.; Jansky, Liz J.; Harniss, Mark; Riley, William

2013-01-01

Introduction The National Institutes of Health sponsored Patient-Reported Outcome Measurement Information System (PROMIS) aimed to create item banks and computerized adaptive tests (CATs) across multiple domains for individuals with a range of chronic diseases. Purpose Web-based software was created to enable a researcher to create study-specific Websites that could administer PROMIS CATs and other instruments to research participants or clinical samples. This paper outlines the process used to develop a user-friendly, free, Web-based resource (Assessment CenterSM) for storage, retrieval, organization, sharing, and administration of patient-reported outcomes (PRO) instruments. Methods Joint Application Design (JAD) sessions were conducted with representatives from numerous institutions in order to supply a general wish list of features. Use Cases were then written to ensure that end user expectations matched programmer specifications. Program development included daily programmer “scrum” sessions, weekly Usability Acceptability Testing (UAT) and continuous Quality Assurance (QA) activities pre- and post-release. Results Assessment Center includes features that promote instrument development including item histories, data management, and storage of statistical analysis results. Conclusions This case study of software development highlights the collection and incorporation of user input throughout the development process. Potential future applications of Assessment Center in clinical research are discussed. PMID:20306332

College of American Pathologists' laboratory standards for next-generation sequencing clinical tests.

PubMed

Aziz, Nazneen; Zhao, Qin; Bry, Lynn; Driscoll, Denise K; Funke, Birgit; Gibson, Jane S; Grody, Wayne W; Hegde, Madhuri R; Hoeltge, Gerald A; Leonard, Debra G B; Merker, Jason D; Nagarajan, Rakesh; Palicki, Linda A; Robetorye, Ryan S; Schrijver, Iris; Weck, Karen E; Voelkerding, Karl V

2015-04-01

The higher throughput and lower per-base cost of next-generation sequencing (NGS) as compared to Sanger sequencing has led to its rapid adoption in clinical testing. The number of laboratories offering NGS-based tests has also grown considerably in the past few years, despite the fact that specific Clinical Laboratory Improvement Amendments of 1988/College of American Pathologists (CAP) laboratory standards had not yet been developed to regulate this technology. To develop a checklist for clinical testing using NGS technology that sets standards for the analytic wet bench process and for bioinformatics or "dry bench" analyses. As NGS-based clinical tests are new to diagnostic testing and are of much greater complexity than traditional Sanger sequencing-based tests, there is an urgent need to develop new regulatory standards for laboratories offering these tests. To develop the necessary regulatory framework for NGS and to facilitate appropriate adoption of this technology for clinical testing, CAP formed a committee in 2011, the NGS Work Group, to deliberate upon the contents to be included in the checklist. Results . -A total of 18 laboratory accreditation checklist requirements for the analytic wet bench process and bioinformatics analysis processes have been included within CAP's molecular pathology checklist (MOL). This report describes the important issues considered by the CAP committee during the development of the new checklist requirements, which address documentation, validation, quality assurance, confirmatory testing, exception logs, monitoring of upgrades, variant interpretation and reporting, incidental findings, data storage, version traceability, and data transfer confidentiality.

Visual Impairment/lntracranial Pressure Risk Clinical Care Data Tools

NASA Technical Reports Server (NTRS)

Van Baalen, Mary; Mason, Sara S.; Taiym, Wafa; Wear, Mary L.; Moynihan, Shannan; Alexander, David; Hart, Steve; Tarver, William

2014-01-01

Prior to 2010, several ISS crewmembers returned from spaceflight with changes to their vision, ranging from a mild hyperopic shift to frank disc edema. As a result, NASA expanded clinical vision testing to include more comprehensive medical imaging, including Optical Coherence Tomography and 3 Tesla Brain and Orbit MRIs. The Space and Clinical Operations (SCO) Division developed a clinical practice guideline that classified individuals based on their symptoms and diagnoses to facilitate clinical care. For the purposes of clinical surveillance, this classification was applied retrospectively to all crewmembers who had sufficient testing for classification. This classification is also a tool that has been leveraged for researchers to identify potential risk factors. In March 2014, driven in part by a more comprehensive understanding of the imaging data and increased imaging capability on orbit, the SCO Division revised their clinical care guidance to outline in-flight care and increase post-flight follow up. The new clinical guidance does not include a classification scheme

Assessment of cognitive safety in clinical drug development

PubMed Central

Roiser, Jonathan P.; Nathan, Pradeep J.; Mander, Adrian P.; Adusei, Gabriel; Zavitz, Kenton H.; Blackwell, Andrew D.

2016-01-01

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks. PMID:26610416

Core competencies in clinical neuropsychology training across the world.

PubMed

Hessen, Erik; Hokkanen, Laura; Ponsford, Jennie; van Zandvoort, Martine; Watts, Ann; Evans, Jonathan; Haaland, Kathleen Y

2018-05-01

This work aimed to review main competency requirements from training models in countries with well-established specialties in clinical neuropsychology and to extract core competencies that likely will apply to clinical neuropsychologists regardless of regional and cultural context. We reviewed standards for post-graduate training in clinical neuropsychology from countries in Europe, Australia, and North America based on existing literature, presentations at international conferences, and from description of the training models from national psychological or neuropsychological associations. Despite differences, the reviewed models share similar core competencies considered necessary for a specialty in clinical neuropsychology: (1) In-depth knowledge of general psychology including clinical psychology (post-graduate level), ethical, and legal standards. (2) Expert knowledge about clinically relevant brain-behavioral relationships. (3) Comprehensive knowledge about, and skills in, related clinical disciplines. (4) In-depth knowledge about and skills in neuropsychological assessment, including decision-making and diagnostic competency according to current classification of diseases. (5) Competencies in the area of diversity and culture in relation to clinical neuropsychology. (6) Communication competency of neuropsychological findings and test results to relevant and diverse audiences. (7) Knowledge about and skills in psychological and neuropsychological intervention, including treatment and rehabilitation. All the models have undergone years of development in accordance with requirements of national health care systems in different parts of the world. Despite differences, the common core competency requirements across different regions of the world suggest generalizability of these competencies. We hope this summary can be useful as countries with less established neuropsychology training programs develop their models.

Assessing Professionalism: A Theoretical Framework for Defining Clinical Rotation Assessment Criteria.

PubMed

Armitage-Chan, Elizabeth

Although widely accepted as an important graduate competence, professionalism is a challenging outcome to define and assess. Clinical rotations provide an excellent opportunity to develop student professionalism through the use of experiential learning and effective feedback, but without appropriate theoretical frameworks, clinical teachers may find it difficult to identify appropriate learning outcomes. The adage "I know it when I see it" is unhelpful in providing feedback and guidance for student improvement, and criteria that are more specifically defined would help students direct their own development. This study sought first to identify how clinical faculty in one institution currently assess professionalism, using retrospective analysis of material obtained in undergraduate teaching and faculty development sessions. Subsequently, a faculty workshop was held in which a round-table type discussion sought to develop these ideas and identify how professionalism assessment could be improved. The output of this session was a theoretical framework for teaching and assessing professionalism, providing example assessment criteria and ideas for clinical teaching. This includes categories such as client and colleague interaction, respect and trust, recognition of limitations, and understanding of different professional identities. Each category includes detailed descriptions of the knowledge, skills, and behaviors expected of students in these areas. The criteria were determined by engaging faculty in the development of the framework, and therefore they should represent a focused development of criteria already used to assess professionalism, and not a novel and unfamiliar set of assessment guidelines. The faculty-led nature of this framework is expected to facilitate implementation in clinical teaching.

Clinical leadership in contemporary clinical practice: implications for nursing in Australia.

PubMed

Davidson, P M; Elliott, D; Daly, J

2006-04-01

Leadership in the clinical practice environment is important to ensure both optimal patient outcomes and successive generations of motivated and enthusiastic clinicians. The present paper seeks to define and describe clinical leadership and identify the facilitators and barriers to clinical leadership. We also describe strategies to develop clinical leaders in Australia. Key drivers to the development of nursing leaders are strategies that recognize and value clinical expertise. These include models of care that highlight the importance of the nursing role; evidence-based practice and measurement of clinical outcomes; strategies to empower clinicians and mechanisms to ensure participation in clinical decision-making. Significant barriers to clinical leadership are organizational structures that preclude nurses from clinical decision making; the national shortage of nurses; fiscal constraints; absence of well evaluated models of care and trends towards less skilled clinicians. Systematic, strategic initiatives are required to nurture and develop clinical leaders. These strategies need to be collegial collaborations between the academic and health care sectors in order to provide a united voice for advancing the nursing profession.

Automation of CT-based haemorrhagic stroke assessment for improved clinical outcomes: study protocol and design

PubMed Central

Chinda, Betty; Medvedev, George; Siu, William; Ester, Martin; Arab, Ali; Gu, Tao; Moreno, Sylvain; D’Arcy, Ryan C N; Song, Xiaowei

2018-01-01

Introduction Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors’ quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Methods and analysis Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. Ethics and dissemination The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging scientists, computing scientists and clinical professionals in neurology and neuroradiology and includes patient representatives. Research outputs will be disseminated following knowledge translation plans towards improving stroke patient care. Significant findings will be published in scientific journals. Anticipated deliverables include computer solutions for improved clinical assessment of haematoma using NCCT. PMID:29674371

Exploring the Link between Self-Efficacy, Workplace Learning and Clinical Practice

ERIC Educational Resources Information Center

Cox, Jennifer; Simpson, Maree Donna

2016-01-01

Pre-registration nurse education includes both conceptual and practical elements to prepare graduates for the transition to clinical practice. Workplace learning plays an important role in developing students' confidence, clinical skills and competency. This paper explores the, perhaps overlooked, centrality of self-efficacy to all areas of…

Structuring a Clinical Learning Environment for a Hybrid-PBL Dental Curriculum.

ERIC Educational Resources Information Center

MacNeil, M. A. J.; Walton, Joanne N.; Clark, D. Christopher; Tobias, David L.; Harrison, Rosamund L.

1998-01-01

Describes the evolution and implementation of a joint medical-dental problem-based learning (PBL) curriculum at the University of British Columbia's medical and dental schools, featuring development of an integrated care clinic. Issues in structuring the new curriculum are discussed, including management of the clinic's group practices, affective…

Building Trust.

ERIC Educational Resources Information Center

Ambler, Marjane

1994-01-01

Describes how an initial $1,500 grant helped build a desperately needed health clinic on the Pine Ridge Reservation. Provides the history of the clinic, from its beginning as a small grant to its ultimate development into a $400,000 solar-heated health clinic with a staff of 9 people, including a full-time physician. (MAB)

Developing an evidence-based practice protocol: implications for midwifery practice.

PubMed

Carr, K C

2000-01-01

Evidence-based practice is defined and its importance to midwifery practice is presented. Guidelines are provided for the development of an evidence-based practice protocol. These include: identifying the clinical question, obtaining the evidence, evaluating the validity and importance of the evidence, synthesizing the evidence and applying it to the development of a protocol or clinical algorithm, and, finally, developing an evaluation plan or measurement strategy to see if the new protocol is effective.

Technology, design and dementia: an exploratory survey of developers.

PubMed

Jiancaro, Tizneem; Jaglal, Susan B; Mihailidis, Alex

2017-08-01

Despite worldwide surges in dementia, we still know relatively little about the design of home technologies that support this population. The purpose of this study was to investigate design considerations from the perspective of developers. Participants, including technical and clinical specialists, were recruited internationally and answered web-based survey questions comprising Likert-type responses with text entry options. Developers were queried on 23 technology acceptance characteristics and 24 design practices. In all, forty developers completed the survey. Concerning "technology acceptance", cost, learnability, self-confidence (during use) and usability were deemed very important. Concerning "design practice", developers overwhelmingly valued user-centred design (UCD). In terms of general assistive technology (AT) models, these were largely unknown by technical specialists compared to clinical specialists. Recommendations based on this study include incorporating "self-confidence" into design protocols; examining the implications of "usability" and UCD in this context; and considering empathy-based design approaches to suit a diverse user population. Moreover, clinical specialists have much to offer development teams, particularly concerning the use of conceptual AT models. Implications of rehabilitation Stipulate precise usability criteria. Consider "learnability" and "self-confidence" as technology adoption criteria. Recognize the important theoretical role that clinical specialists can fulfil concerning the use of design schemas. Acknowledge the diversity amongst users with dementia, potentially adopting techniques, such as designing for "extraordinary users".

Precision medicine in oncology: New practice models and roles for oncology pharmacists.

PubMed

Walko, Christine; Kiel, Patrick J; Kolesar, Jill

2016-12-01

Three different precision medicine practice models developed by oncology pharmacists are described, including strategies for implementation and recommendations for educating the next generation of oncology pharmacy practitioners. Oncology is unique in that somatic mutations can both drive the development of a tumor and serve as a therapeutic target for treating the cancer. Precision medicine practice models are a forum through which interprofessional teams, including pharmacists, discuss tumor somatic mutations to guide patient-specific treatment. The University of Wisconsin, Indiana University, and Moffit Cancer Center have implemented precision medicine practice models developed and led by oncology pharmacists. Different practice models, including a clinic, a clinical consultation service, and a molecular tumor board (MTB), were adopted to enhance integration into health systems and payment structures. Although the practice models vary, commonalities of three models include leadership by the clinical pharmacist, specific therapeutic recommendations, procurement of medications for off-label use, and a research component. These three practice models function as interprofessional training sites for pharmacy and medical students and residents, providing an important training resource at these institutions. Key implementation strategies include interprofessional involvement, institutional support, integration into clinical workflow, and selection of model by payer mix. MTBs are a pathway for clinical implementation of genomic medicine in oncology and are an emerging practice model for oncology pharmacists. Because pharmacists must be prepared to participate fully in contemporary practice, oncology pharmacy residents must be trained in genomic oncology, schools of pharmacy should expand precision medicine and genomics education, and opportunities for continuing education in precision medicine should be made available to practicing pharmacists. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Industry Perspective of Pediatric Drug Development in the United States: Involvement of the European Union Countries.

PubMed

Onishi, Taku; Tsukamoto, Katsura; Matsumaru, Naoki; Waki, Takashi

2018-01-01

Efforts to promote the development of pediatric pharmacotherapy include regulatory frameworks and close collaboration between the US Food and Drug Administration and the European Medicines Agency. We characterized the current status of pediatric clinical trials conducted in the United States by the pharmaceutical industry, focusing on the involvement of the European Union member countries, to clarify the industry perspective. Data on US pediatric clinical trials were obtained from ClinicalTrials.gov . Binary regression analysis was performed to identify what factors influence the likelihood of involvement of European Union countries. A total of 633 US pediatric clinical trials that met inclusion criteria were extracted and surveyed. Of these, 206 (32.5%) involved a European Union country site(s). The results of binary regression analysis indicated that attribution of industry, phase, disease area, and age of pediatric participants influenced the likelihood of the involvement of European Union countries in US pediatric clinical trials. Relatively complicated or large pediatric clinical trials, such as phase II and III trials and those that included a broad age range of participants, had a significantly greater likelihood of the involvement of European Union countries ( P < .05). Our results suggest that (1) the pharmaceutical industry utilizes regulatory frameworks in making business decisions regarding pediatric clinical trials, (2) disease area affects the involvement of European Union countries, and (3) feasibility of clinical trials is mainly concerned by pharmaceutical industry for pediatric drug development. Additional incentives for high marketability may further motivate pharmaceutical industry to develop pediatric drugs.

Holding up a mirror: changing obstetric practice through criterion-based clinical audit in developing countries.

PubMed

Wagaarachchi, P T; Graham, W J; Penney, G C; McCaw-Binns, A; Yeboah Antwi, K; Hall, M H

2001-08-01

The objective of the study described is to assess the feasibility and effectiveness of using a criterion-based clinical audit to measure and improve the quality of obstetric care at the district hospital level in developing countries. The focus is on the management of five life-threatening obstetric complications--hemorrhage, eclampsia, genital tract infection, obstructed labor and uterine rupture was audited using a "before and after" design. The five steps of the audit cycle were followed: establish criteria of good quality care; measure current practice (Review I); feedback findings and set targets; take action to change practice; and re-evaluate practice (Review II). Systematic literature review, panel discussions and pilot work led to the development of 31 audit criteria. Review I included 555 life-threatening complications occurring over 66 hospital-months; Review II included 342 complications over 42 hospital-months. Many common areas for improvement were identified across the four hospitals. Agreed mechanisms for achieving these improvements included clinical protocols, reviews of staffing, and training workshops. Some aspects of clinical monitoring, drug use and record keeping improved significantly between Reviews I and II. Criterion-based clinical audit in four typical district hospitals in Ghana and Jamaica is a feasible and acceptable method for quality assurance and appears to have improved the management of life-threatening obstetric complications.

Identifying clinical features in primary care electronic health record studies: methods for codelist development.

PubMed

Watson, Jessica; Nicholson, Brian D; Hamilton, Willie; Price, Sarah

2017-11-22

Analysis of routinely collected electronic health record (EHR) data from primary care is reliant on the creation of codelists to define clinical features of interest. To improve scientific rigour, transparency and replicability, we describe and demonstrate a standardised reproducible methodology for clinical codelist development. We describe a three-stage process for developing clinical codelists. First, the clear definition a priori of the clinical feature of interest using reliable clinical resources. Second, development of a list of potential codes using statistical software to comprehensively search all available codes. Third, a modified Delphi process to reach consensus between primary care practitioners on the most relevant codes, including the generation of an 'uncertainty' variable to allow sensitivity analysis. These methods are illustrated by developing a codelist for shortness of breath in a primary care EHR sample, including modifiable syntax for commonly used statistical software. The codelist was used to estimate the frequency of shortness of breath in a cohort of 28 216 patients aged over 18 years who received an incident diagnosis of lung cancer between 1 January 2000 and 30 November 2016 in the Clinical Practice Research Datalink (CPRD). Of 78 candidate codes, 29 were excluded as inappropriate. Complete agreement was reached for 44 (90%) of the remaining codes, with partial disagreement over 5 (10%). 13 091 episodes of shortness of breath were identified in the cohort of 28 216 patients. Sensitivity analysis demonstrates that codes with the greatest uncertainty tend to be rarely used in clinical practice. Although initially time consuming, using a rigorous and reproducible method for codelist generation 'future-proofs' findings and an auditable, modifiable syntax for codelist generation enables sharing and replication of EHR studies. Published codelists should be badged by quality and report the methods of codelist generation including: definitions and justifications associated with each codelist; the syntax or search method; the number of candidate codes identified; and the categorisation of codes after Delphi review. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Knowledge Translation in Audiology

PubMed Central

Kothari, Anita; Bagatto, Marlene P.; Seewald, Richard; Miller, Linda T.; Scollie, Susan D.

2011-01-01

The impetus for evidence-based practice (EBP) has grown out of widespread concern with the quality, effectiveness (including cost-effectiveness), and efficiency of medical care received by the public. Although initially focused on medicine, EBP principles have been adopted by many of the health care professions and are often represented in practice through the development and use of clinical practice guidelines (CPGs). Audiology has been working on incorporating EBP principles into its mandate for professional practice since the mid-1990s. Despite widespread efforts to implement EBP and guidelines into audiology practice, gaps still exist between the best evidence based on research and what is being done in clinical practice. A collaborative dynamic and iterative integrated knowledge translation (KT) framework rather than a researcher-driven hierarchical approach to EBP and the development of CPGs has been shown to reduce the knowledge-to-clinical action gaps. This article provides a brief overview of EBP and CPGs, including a discussion of the barriers to implementing CPGs into clinical practice. It then offers a discussion of how an integrated KT process combined with a community of practice (CoP) might facilitate the development and dissemination of evidence for clinical audiology practice. Finally, a project that uses the knowledge-to-action (KTA) framework for the development of outcome measures in pediatric audiology is introduced. PMID:22194314

Treatment of the Biracial Child: Theoretical and Clinical Issues.

ERIC Educational Resources Information Center

Brandell, Jerrold R.

1988-01-01

Discusses theoretical and clinical issues that surround the psychotherapeutic treatment of biracial children. Summarizes Heinz Kohut's theory on the development of the self in the biracial child. A case study is included. (BH)

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists

PubMed Central

Boycott, Kym; Hartley, Taila; Adam, Shelin; Bernier, Francois; Chong, Karen; Fernandez, Bridget A; Friedman, Jan M; Geraghty, Michael T; Hume, Stacey; Knoppers, Bartha M; Laberge, Anne-Marie; Majewski, Jacek; Mendoza-Londono, Roberto; Meyn, M Stephen; Michaud, Jacques L; Nelson, Tanya N; Richer, Julie; Sadikovic, Bekim; Skidmore, David L; Stockley, Tracy; Taylor, Sherry; van Karnebeek, Clara; Zawati, Ma'n H; Lauzon, Julie; Armour, Christine M

2015-01-01

Purpose and scope The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally. PMID:25951830

New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review.

PubMed

Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S

2015-09-01

The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice.

Clinical development of Ebola vaccines

PubMed Central

Sridhar, Saranya

2015-01-01

The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

Defining Outcome Measures for Psoriasis: The IDEOM Report from the GRAPPA 2016 Annual Meeting.

PubMed

Callis Duffin, Kristina; Gottlieb, Alice B; Merola, Joseph F; Latella, John; Garg, Amit; Armstrong, April W

2017-05-01

The International Dermatology Outcome Measures (IDEOM) psoriasis working group was established to develop core domains and measurements sets for psoriasis clinical trials and ultimately clinical practice. At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the IDEOM psoriasis group presented an overview of its progress toward developing this psoriasis core domain set. First, it summarized the February 2016 meeting of all involved with the IDEOM, highlighting patient and payer perspectives on outcome measures. Second, the group presented an overview of the consensus process for developing the core domain set for psoriasis, including previous literature reviews, nominal group exercises, and meeting discussions. Future plans include the development of working groups to review candidate measures for at least 2 of the domains, including primary pathophysiologic manifestations and patient-reported outcomes, and Delphi surveys to gain consensus on the final psoriasis core domain set.

Implications of pharmacogenomics for drug development and clinical practice.

PubMed

Ginsburg, Geoffrey S; Konstance, Richard P; Allsbrook, Jennifer S; Schulman, Kevin A

2005-11-14

Pharmacogenomics is likely to be among the first clinical applications of the Human Genome Project and is certain to have an enormous impact on the clinical practice of medicine. Herein, we discuss the potential implications of pharmacogenomics on the drug development process, including drug safety, productivity, market segmentation, market expansion, differentiation, and personalized health care. We also review 3 challenges facing the translation of pharmacogenomics into clinical practice: dependence on information technology, limited health care financing, and the scientific uncertainty surrounding validation of specific applications of the technology. To our knowledge, there is currently no formal agenda to promote and cultivate innovation, to develop progressive information technology, or to obtain the financing that would be required to advance the use of pharmacogenomic technologies in patient care. Although the potential of these technologies is driving change in the development of clinical sciences, it remains to be seen which health care systems level needs will be addressed.

Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians.

PubMed

Qaseem, Amir; McLean, Robert M; Starkey, Melissa; Forciea, Mary Ann

2017-01-03

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the diagnosis of gout. This guideline is based on a systematic review of published studies on gout diagnosis, identified using several databases, from database inception to February 2016. Evaluated outcomes included the accuracy of the test results; intermediate outcomes (results of laboratory and radiographic tests, such as serum urate and synovial fluid crystal analysis and radiographic or ultrasonography changes); clinical decision making (additional testing and pharmacologic or dietary management); short-term clinical (patient-centered) outcomes, such as pain and joint swelling and tenderness; and adverse effects of the tests. This guideline grades the evidence and recommendations by using the ACP grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. The target audience for this guideline includes all clinicians, and the target patient population includes adults with joint inflammation suspected to be gout. ACP recommends that clinicians use synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible acute gout. (Grade: weak recommendation, low-quality evidence).

A novel mentorship programme for residents integrating academic development, clinical teaching and graduate medical education assessment.

PubMed

Bhatia, Kriti; Takayesu, James Kimo; Nadel, Eric S

2016-02-01

Mentorship fosters career development and growth. During residency training, mentorship should support clinical development along with intellectual and academic interests. Reported resident mentoring programmes do not typically include clinical components. We designed a programme that combines academic development with clinical feedback and assessment in a four-year emergency medicine residency programme. Incoming interns were assigned an advisor. At the conclusion of the intern year, residents actively participated in selecting a mentor for the duration of residency. The programme consisted of quarterly meetings, direct clinical observation and specific competency assessment, assistance with lecture preparation, real-time feedback on presentations, simulation coaching sessions, and discussions related to career development. Faculty participation was recognized as a valuable component of the annual review process. Residents were surveyed about the overall programme and individual components. Over 88 % of the respondents said that the programme was valuable and should be continued. Senior residents most valued the quarterly meetings and presentation help and feedback. Junior residents strongly valued the clinical observation and simulation sessions. A comprehensive mentorship programme integrating clinical, professional and academic development provides residents individualized feedback and coaching and is valued by trainees. Individualized assessment of clinical competencies can be conducted through such a programme.

Developing clinically suitable measures of social cognition for children: initial findings from a normative sample.

PubMed

Saltzman-Benaiah, Jennifer; Lalonde, Christopher E

2007-03-01

Our understanding of children's social competence has increased tremendously over the past two decades. There is increasing evidence to suggest that social-cognitive impairments are not restricted to children on the autistic spectrum, but rather may be associated with a host of developmental and acquired neurological conditions including learning disabilities, attention deficit disorder, traumatic brain injury, and stroke. Although many investigators have begun to bridge the gap between clinical practice and research by applying experimental tasks to clinical populations, few tools are available for the clinical evaluation of social competence, particularly in children. This study marks a series of first steps in the development of measures suitable for the assessment of children between 6 and 12 years of age. The results of the study provide data for a number of experimental tasks that have been adapted with clinical practice in mind. A discussion of the developmental progressions and the relationships among the measures is also included.

Perspective: Recommendations for benchmarking pre-clinical studies of nanomedicines

PubMed Central

Dawidczyk, Charlene M.; Russell, Luisa M.; Searson, Peter C.

2015-01-01

Nanoparticle-based delivery systems provide new opportunities to overcome the limitations associated with traditional small molecule drug therapy for cancer, and to achieve both therapeutic and diagnostic functions in the same platform. Pre-clinical trials are generally designed to assess therapeutic potential and not to optimize the design of the delivery platform. Consequently, progress in developing design rules for cancer nanomedicines has been slow, hindering progress in the field. Despite the large number of pre-clinical trials, several factors restrict comparison and benchmarking of different platforms, including variability in experimental design, reporting of results, and the lack of quantitative data. To solve this problem, we review the variables involved in the design of pre-clinical trials and propose a protocol for benchmarking that we recommend be included in in vivo pre-clinical studies of drug delivery platforms for cancer therapy. This strategy will contribute to building the scientific knowledge base that enables development of design rules and accelerates the translation of new technologies. PMID:26249177

Drugs, money and society (Part II).

PubMed

Walley, Tom

2010-09-01

Pharmacoeconomics started as marketing but has developed into a valuable tool in the fuller assessment of drug therapies. Its principles are now widely accepted, and many countries have government-funded agencies with responsibility for its application, most notably the National Institute for Health and Clinical Excellence in England. Many clinical pharmacologists are active in this area, and the discipline itself is part of the clinical pharmacology trainees' curriculum. Further developments will include value-based pricing and its use in cost sharing arrangements between health service and manufacturers.

Clinical Core Competency Training for NASA Flight Surgeons

NASA Technical Reports Server (NTRS)

Polk, J. D.; Schmid, Josef; Hurst, Victor, IV; Doerr, Harold K.; Doerr, Harold K.

2007-01-01

Introduction: The cohort of NASA flight surgeons (FS) is a very accomplished group with varied clinical backgrounds; however, the NASA Flight Surgeon Office has identified that the extremely demanding schedule of this cohort prevents many of these physicians from practicing clinical medicine on a regular basis. In an effort to improve clinical competency, the NASA FS Office has dedicated one day a week for the FS to receive clinical training. Each week, an FS is assigned to one of five clinical settings, one being medical patient simulation. The Medical Operations Support Team (MOST) was tasked to develop curricula using medical patient simulation that would meet the clinical and operational needs of the NASA FS Office. Methods: The MOST met with the Lead FS and Training Lead FS to identify those core competencies most important to the FS cohort. The MOST presented core competency standards from the American Colleges of Emergency Medicine and Internal Medicine as a basis for developing the training. Results: The MOST identified those clinical areas that could be best demonstrated and taught using medical patient simulation, in particular, using high fidelity human patient simulators. Curricula are currently being developed and additional classes will be implemented to instruct the FS cohort. The curricula will incorporate several environments for instruction, including lab-based and simulated microgravity-based environments. Discussion: The response from the NASA FS cohort to the initial introductory class has been positive. As a result of this effort, the MOST has identified three types of training to meet the clinical needs of the FS Office; clinical core competency training, individual clinical refresher training, and just-in-time training (specific for post-ISS Expedition landings). The MOST is continuing to work with the FS Office to augment the clinical training for the FS cohort, including the integration of Web-based learning.

Developing an International Register of Clinical Prediction Rules for Use in Primary Care: A Descriptive Analysis

PubMed Central

Keogh, Claire; Wallace, Emma; O’Brien, Kirsty K.; Galvin, Rose; Smith, Susan M.; Lewis, Cliona; Cummins, Anthony; Cousins, Grainne; Dimitrov, Borislav D.; Fahey, Tom

2014-01-01

PURPOSE We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. METHODS To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. RESULTS Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study), resulting in 989 individual studies. In all, 434 unique rules had gone through derivation; however, only 54.8% had been validated and merely 2.8% had undergone analysis of their impact on either the process or outcome of clinical care. The rules most commonly pertained to cardiovascular disease, respiratory, and musculoskeletal conditions. They had most often been studied in the primary care or emergency department settings. CONCLUSIONS Many clinical prediction rules have been derived, but only about half have been validated and few have been assessed for clinical impact. This lack of thorough evaluation for many rules makes it difficult to retrieve and identify those that are ready for use at the point of patient care. We plan to develop an international web-based register of clinical prediction rules and computer-based clinical decision support systems. PMID:25024245

Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for ‘point of care’ management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. Design/methods We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma—the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis—the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process evaluation to assess the implementation strategy and an economic analysis to evaluate implementation costs and benefits. Discussion This study will contribute to the body of evidence supporting effective strategies for clinical pathway implementation, and ultimately reducing the research to practice gaps by operationalizing best evidence care recommendations through effective use of clinical pathways. Trial registration ClinicalTrials.gov: NCT01815710 PMID:23692634

Creating a Longitudinal Integrated Clerkship with Mutual Benefits for an Academic Medical Center and a Community Health System

PubMed Central

Poncelet, Ann Noelle; Mazotti, Lindsay A; Blumberg, Bruce; Wamsley, Maria A; Grennan, Tim; Shore, William B

2014-01-01

The longitudinal integrated clerkship is a model of clinical education driven by tenets of social cognitive theory, situated learning, and workplace learning theories, and built on a foundation of continuity between students, patients, clinicians, and a system of care. Principles and goals of this type of clerkship are aligned with primary care principles, including patient-centered care and systems-based practice. Academic medical centers can partner with community health systems around a longitudinal integrated clerkship to provide mutual benefits for both organizations, creating a sustainable model of clinical training that addresses medical education and community health needs. A successful one-year longitudinal integrated clerkship was created in partnership between an academic medical center and an integrated community health system. Compared with traditional clerkship students, students in this clerkship had better scores on Clinical Performance Examinations, internal medicine examinations, and high perceptions of direct observation of clinical skills. Advantages for the academic medical center include mitigating the resources required to run a longitudinal integrated clerkship while providing primary care training and addressing core competencies such as systems-based practice, practice-based learning, and interprofessional care. Advantages for the community health system include faculty development, academic appointments, professional satisfaction, and recruitment. Success factors include continued support and investment from both organizations’ leadership, high-quality faculty development, incentives for community-based physician educators, and emphasis on the mutually beneficial relationship for both organizations. Development of a longitudinal integrated clerkship in a community health system can serve as a model for developing and expanding these clerkship options for academic medical centers. PMID:24867551

Creating a longitudinal integrated clerkship with mutual benefits for an academic medical center and a community health system.

PubMed

Poncelet, Ann Noelle; Mazotti, Lindsay A; Blumberg, Bruce; Wamsley, Maria A; Grennan, Tim; Shore, William B

2014-01-01

The longitudinal integrated clerkship is a model of clinical education driven by tenets of social cognitive theory, situated learning, and workplace learning theories, and built on a foundation of continuity between students, patients, clinicians, and a system of care. Principles and goals of this type of clerkship are aligned with primary care principles, including patient-centered care and systems-based practice. Academic medical centers can partner with community health systems around a longitudinal integrated clerkship to provide mutual benefits for both organizations, creating a sustainable model of clinical training that addresses medical education and community health needs. A successful one-year longitudinal integrated clerkship was created in partnership between an academic medical center and an integrated community health system. Compared with traditional clerkship students, students in this clerkship had better scores on Clinical Performance Examinations, internal medicine examinations, and high perceptions of direct observation of clinical skills.Advantages for the academic medical center include mitigating the resources required to run a longitudinal integrated clerkship while providing primary care training and addressing core competencies such as systems-based practice, practice-based learning, and interprofessional care. Advantages for the community health system include faculty development, academic appointments, professional satisfaction, and recruitment.Success factors include continued support and investment from both organizations' leadership, high-quality faculty development, incentives for community-based physician educators, and emphasis on the mutually beneficial relationship for both organizations. Development of a longitudinal integrated clerkship in a community health system can serve as a model for developing and expanding these clerkship options for academic medical centers.

Pragmatic characteristics of patient-reported outcome measures are important for use in clinical practice.

PubMed

Kroenke, Kurt; Monahan, Patrick O; Kean, Jacob

2015-09-01

Measures for assessing patient-reported outcomes (PROs) that may have initially been developed for research are increasingly being recommended for use in clinical practice as well. Although psychometric rigor is essential, this article focuses on pragmatic characteristics of PROs that may enhance uptake into clinical practice. Three sources were drawn on in identifying pragmatic criteria for PROs: (1) selected literature review including recommendations by other expert groups; (2) key features of several model public domain PROs; and (3) the authors' experience in developing practical PROs. Eight characteristics of a practical PRO include: (1) actionability (i.e., scores guide diagnostic or therapeutic actions/decision making); (2) appropriateness for the relevant clinical setting; (3) universality (i.e., for screening, severity assessment, and monitoring across multiple conditions); (4) self-administration; (5) item features (number of items and bundling issues); (6) response options (option number and dimensions, uniform vs. varying options, time frame, intervals between options); (7) scoring (simplicity and interpretability); and (8) accessibility (nonproprietary, downloadable, available in different languages and for vulnerable groups, and incorporated into electronic health records). Balancing psychometric and pragmatic factors in the development of PROs is important for accelerating the incorporation of PROs into clinical practice. Published by Elsevier Inc.

Risk Prediction Models for Acute Kidney Injury in Critically Ill Patients: Opus in Progressu.

PubMed

Neyra, Javier A; Leaf, David E

2018-05-31

Acute kidney injury (AKI) is a complex systemic syndrome associated with high morbidity and mortality. Among critically ill patients admitted to intensive care units (ICUs), the incidence of AKI is as high as 50% and is associated with dismal outcomes. Thus, the development and validation of clinical risk prediction tools that accurately identify patients at high risk for AKI in the ICU is of paramount importance. We provide a comprehensive review of 3 clinical risk prediction tools that have been developed for incident AKI occurring in the first few hours or days following admission to the ICU. We found substantial heterogeneity among the clinical variables that were examined and included as significant predictors of AKI in the final models. The area under the receiver operating characteristic curves was ∼0.8 for all 3 models, indicating satisfactory model performance, though positive predictive values ranged from only 23 to 38%. Hence, further research is needed to develop more accurate and reproducible clinical risk prediction tools. Strategies for improved assessment of AKI susceptibility in the ICU include the incorporation of dynamic (time-varying) clinical parameters, as well as biomarker, functional, imaging, and genomic data. © 2018 S. Karger AG, Basel.

Implementing a Gerontological Clinical Nursing Practice with an Interdisciplinary Focus: Lessons Learned

ERIC Educational Resources Information Center

Dahlke, Sherry; Fehr, Cindy

2010-01-01

A gerontological clinical nursing practice with an interdisciplinary focus was developed to provide opportunities for student nurses to expand their knowledge about aging, hone assessment skills, and critically examine beliefs about older adults. The practice included theory about older adults and a rotation through a variety of clinical settings…

Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients.

PubMed

Thom, Claire

2015-09-01

Claire Thom speaks to Gemma Westcott, Commissioning Editor: Claire Thom joined Astellas in 2013 as the Therapeutic Area Head for Oncology in Global Development. In that role, she also serves as the STAR leader for Oncology for Astellas. Prior to Astellas, she spent 12 years with Takeda. Her last position was Senior Vice President, Portfolio Management, Drug Development Management and Medical Informatics and Strategic Operations within the Medical Division (the Division within Millennium responsible for oncology clinical drug development within Takeda). During her 4 years at Millennium, at various times, she had responsibility within the Medical Division for leading portfolio management, business operations (medical finance, annual and mid-range financial planning, space planning and operations, headcount resourcing, development goals process), clinical development operations (clinical operations, programming, data management, statistics, medical writing, clinical outsourcing), drug development management (project management), medical informatics (technology support for the division) and the strategic project management office for the division. Prior to joining Millennium, Claire Thom spent 18 months working in Osaka, Japan, during which she was responsible for developing the oncology strategy for Takeda that culminated in the acquisition of Millennium. Before going to Japan, she held positions of varying responsibility within the Takeda US development organization including the management of regulatory affairs, safety, biometrics and data management, clinical research and quality assurance. Claire Thom has particular expertise in organizational design and efficiency; she has successfully worked through integrations across multiple functions and redesigned business processes. She has a PharmD from University of Illinois (IL, USA) and over 20 years of pharmaceutical experience including positions in medical affairs and new product planning (over 11 years at Searle) and drug development (over 12 years at Takeda/Millennium).

Shoestring budgets, band-AIDS, and team work: challenges and motivators in the development of a Web-based resource for undergraduate clinical skills teaching.

PubMed

Simmons, Collan; Nyhof-Young, Joyce; Bradley, John

2005-05-24

Learning how to conduct a medical interview and perform a physical examination is fundamental to the practice of medicine; however, when this project began, the methods used to teach these skills to medical students at the University of Toronto (U of T) had not changed significantly since the early 1990s despite increasing outpatient care, shorter hospital stays, and heavy preceptor workloads. In response, a Web-based clinical skills resource was developed for the first-year undergraduate medical course-The Art and Science of Clinical Medicine I (ASCM I). This paper examines our experiences with the development of the ASCM I website and details the challenges and motivators inherent in the production of a Web-based, multimedia medical education tool at a large Canadian medical school. Interviews and a focus group were conducted with the development team to discover the factors that positively and negatively affected the development process. Motivating factors included team attributes such as strong leadership and judicious use of medical students and faculty volunteers as developers. Other motivators included a growing lack of instructional equivalency across diverse clinical teaching sites and financial and resource support by the Faculty of Medicine. Barriers to development included an administrative environment that did not yet fully incorporate information technology into its teaching vision and framework, a lack of academic incentive for faculty participation, and inadequate technical support, space, and equipment. The success of electronic educational resources such as the ASCM I website has caused a significant cultural shift within the Faculty of Medicine, resulting in the provision of more space, resources, and support for IT endeavours in the undergraduate medical curriculum.

Considering health equity when moving from evidence-based guideline recommendations to implementation: a case study from an upper-middle income country on the GRADE approach

PubMed Central

Mosquera, Paola; Alzate, Juan Pablo; Pottie, Kevin; Welch, Vivian; Akl, Elie A; Jull, Janet; Lang, Eddy; Katikireddi, Srinivasa Vittal; Morton, Rachel; Thabane, Lehana; Shea, Bev; Stein, Airton T; Singh, Jasvinder; Florez, Ivan D; Guyatt, Gordon; Schünemann, Holger; Tugwell, Peter

2017-01-01

Abstract The availability of evidence-based guidelines does not ensure their implementation and use in clinical practice or policy making. Inequities in health have been defined as those inequalities within or between populations that are avoidable, unnecessary and also unjust and unfair. Evidence-based clinical practice and public health guidelines (‘guidelines’) can be used to target health inequities experienced by disadvantaged populations, although guidelines may unintentionally increase health inequities. For this reason, there is a need for evidence-based clinical practice and public health guidelines to intentionally target health inequities experienced by disadvantaged populations. Current guideline development processes do not include steps for planned implementation of equity-focused guidelines. This article describes nine steps that provide guidance for consideration of equity during guideline implementation. A critical appraisal of the literature followed by a process to build expert consensus was undertaken to define how to include consideration of equity issues during the specific GRADE guideline development process. Using a case study from Colombia we describe nine steps that were used to implement equity-focused GRADE recommendations: (1) identification of disadvantaged groups, (2) quantification of current health inequities, (3) development of equity-sensitive recommendations, (4) identification of key actors for implementation of equity-focused recommendations, (5) identification of barriers and facilitators to the implementation of equity-focused recommendations, (6) development of an equity strategy to be included in the implementation plan, (7) assessment of resources and incentives, (8) development of a communication strategy to support an equity focus and (9) development of monitoring and evaluation strategies. This case study can be used as model for implementing clinical practice guidelines, taking into account equity issues during guideline development and implementation. PMID:29029068

Integrating clinical decision support systems for pharmacogenomic testing into clinical routine - a scoping review of designs of user-system interactions in recent system development.

PubMed

Hinderer, Marc; Boeker, Martin; Wagner, Sebastian A; Lablans, Martin; Newe, Stephanie; Hülsemann, Jan L; Neumaier, Michael; Binder, Harald; Renz, Harald; Acker, Till; Prokosch, Hans-Ulrich; Sedlmayr, Martin

2017-06-06

Pharmacogenomic clinical decision support systems (CDSS) have the potential to help overcome some of the barriers for translating pharmacogenomic knowledge into clinical routine. Before developing a prototype it is crucial for developers to know which pharmacogenomic CDSS features and user-system interactions have yet been developed, implemented and tested in previous pharmacogenomic CDSS efforts and if they have been successfully applied. We address this issue by providing an overview of the designs of user-system interactions of recently developed pharmacogenomic CDSS. We searched PubMed for pharmacogenomic CDSS published between January 1, 2012 and November 15, 2016. Thirty-two out of 118 identified articles were summarized and included in the final analysis. We then compared the designs of user-system interactions of the 20 pharmacogenomic CDSS we had identified. Alerts are the most widespread tools for physician-system interactions, but need to be implemented carefully to prevent alert fatigue and avoid liabilities. Pharmacogenomic test results and override reasons stored in the local EHR might help communicate pharmacogenomic information to other internal care providers. Integrating patients into user-system interactions through patient letters and online portals might be crucial for transferring pharmacogenomic data to external health care providers. Inbox messages inform physicians about new pharmacogenomic test results and enable them to request pharmacogenomic consultations. Search engines enable physicians to compare medical treatment options based on a patient's genotype. Within the last 5 years, several pharmacogenomic CDSS have been developed. However, most of the included articles are solely describing prototypes of pharmacogenomic CDSS rather than evaluating them. To support the development of prototypes further evaluation efforts will be necessary. In the future, pharmacogenomic CDSS will likely include prediction models to identify patients who are suitable for preemptive genotyping.

An update on the clinical evidence that supports biosimilar approvals in Europe.

PubMed

Mielke, Johanna; Jilma, Bernd; Jones, Byron; Koenig, Franz

2018-03-25

Sponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe. We used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars. The high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars. European regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Clinical reasoning of Filipino physical therapists: Experiences in a developing nation.

PubMed

Rotor, Esmerita R; Capio, Catherine M

2018-03-01

Clinical reasoning is essential for physical therapists to engage in the process of client care, and has been known to contribute to professional development. The literature on clinical reasoning and experiences have been based on studies from Western and developed nations, from which multiple influencing factors have been found. A developing nation, the Philippines, has distinct social, economic, political, and cultural circumstances. Using a phenomenological approach, this study explored experiences of Filipino physical therapists on clinical reasoning. Ten therapists working in three settings: 1) hospital; 2) outpatient clinic; and 3) home health were interviewed. Major findings were: a prescription-based referral system limited clinical reasoning; procedural reasoning was a commonly experienced strategy while diagnostic and predictive reasoning were limited; factors that influenced clinical reasoning included practice setting and the professional relationship with the referring physician. Physical therapists' responses suggested a lack of autonomy in practice that appeared to stifle clinical reasoning. Based on our findings, we recommend that the current regulations governing PT practice in the Philippines may be updated, and encourage educators to strengthen teaching approaches and strategies that support clinical reasoning. These recommendations are consistent with the global trend toward autonomous practice.

Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

PubMed Central

Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2015-01-01

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

State-of-the-science of patient navigation as a strategy for enhancing minority clinical trial accrual.

PubMed

Ghebre, Rahel G; Jones, Lovell A; Wenzel, Jennifer A; Martin, Michelle Y; Durant, Raegan W; Ford, Jean G

2014-04-01

Patient navigation programs are emerging that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process as well as outcome measures to evaluate program effectiveness. A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. The eligible studies reported on the development of programs for patient navigation in cancer clinical trials, including training and implementation among African Americans, American Indians, and Native Hawaiians. A low rate of clinical trial refusal (range, 4%-6%) was reported among patients enrolled in patient navigation programs. However, few studies reported on the efficacy of patient navigation in increasing clinical treatment trial enrollment. Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients. © 2014 American Cancer Society.

State-of-the-Science of Patient Navigation as a Strategy for Enhancing Minority Clinical Trial Accrual

PubMed Central

Ghebre, Rahel G.; Jones, Lovell A.; Wenzel, Jennifer; Martin, Michelle Y.; Durant, Raegan; Ford, Jean G.

2014-01-01

Background Patient navigation programs are emerging, that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process, as well as outcome measures to evaluate program effectiveness. Methods A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. Results The eligible studies reported on development of programs for patient navigation in cancer clinical trials, including training and implementation among African American, American Indian and Native Hawaiians. Low clinical trial refusal, 4% to 6%, was reported among patients enrolled in patient navigation program. However, few studies reported on the efficacy of patient navigation on increasing clinical treatment trial enrollment. Conclusion Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients. PMID:24643650

Transmission blocking malaria vaccines: Assays and candidates in clinical development.

PubMed

Sauerwein, R W; Bousema, T

2015-12-22

Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.

A clinical approach to Lyme disease.

PubMed

Nadelman, R B; Wormser, G P

1990-05-01

Lyme disease (also known as Lyme borreliosis) is an emerging, newly described infectious disease with diverse clinical manifestations. The disease is caused by the spirochetal agent Borrelia burgdorferi, which is transmitted to humans by the bite of certain species of Ixodes ticks harboring the organism. The most readily identifiable clinical feature is the distinctive skin lesion, erythema migrans. If recently infected patients go untreated, approximately 15% will develop neurologic conditions (most commonly facial nerve palsy), 8% will develop myocarditis (typically with heart block), and 60% will develop migratory mono- or pauci-articular arthritis. Diagnosis depends on clinical suspicion, recognition of the characteristic signs and symptoms, and appropriate testing for antibody to B. burgdorferi. Serology for Lyme disease, although in need of better standardization, is most useful in diagnosing patients with manifestations of Lyme disease other than erythema migrans. All manifestations of Lyme disease are potentially treatable with either a beta-lactam antibiotic (for instance penicillin, amoxicillin, or ceftriaxone) or a tetracycline preparation. However, the optimal antimicrobial regimen, including choice of drug, drug dose, route of administration, and length of therapy, is unknown. Other important areas for future research include Ixodes biology and control, improved laboratory tests for diagnosis and for assessing response to therapy, and vaccine development.

Interventions to improve patient understanding of cancer clinical trial participation: a systematic review.

PubMed

Kao, C Y; Aranda, S; Krishnasamy, M; Hamilton, B

2017-03-01

Patient misunderstanding of cancer clinical trial participation is identified as a critical issue and researchers have developed and tested a variety of interventions to improve patient understanding. This systematic review identified nine papers published between 2000 and 2013, to evaluate the effects of interventions to improve patient understanding of cancer clinical trial participation. Types of interventions included audio-visual information, revised written information and a communication training workshop. Interventions were conducted alone or in combination with other forms of information provision. The nine papers, all with methodological limitations, reported mixed effects on a small range of outcomes regarding improved patient understanding of cancer clinical trial participation. The methodological limitations included: (1) the intervention development process was poorly described; (2) only a small element of the communication process was addressed; (3) studies lacked evidence regarding what information is essential and critical to enable informed consent; (4) studies lacked reliable and valid outcome measures to show that patients are sufficiently informed to provide consent; and (5) the intervention development process lacked a theoretical framework. Future research needs to consider these factors when developing interventions to improve communication and patient understanding during the informed consent process. © 2016 John Wiley & Sons Ltd.

DianaHealth.com, an On-Line Database Containing Appraisals of the Clinical Value and Appropriateness of Healthcare Interventions: Database Development and Retrospective Analysis.

PubMed

Bonfill, Xavier; Osorio, Dimelza; Solà, Ivan; Pijoan, Jose Ignacio; Balasso, Valentina; Quintana, Maria Jesús; Puig, Teresa; Bolibar, Ignasi; Urrútia, Gerard; Zamora, Javier; Emparanza, José Ignacio; Gómez de la Cámara, Agustín; Ferreira-González, Ignacio

2016-01-01

To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database. Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own. We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice.

Physician participation in clinical research and trials: issues and approaches

PubMed Central

Rahman, Sayeeda; Majumder, Md Anwarul Azim; Shaban, Sami F; Rahman, Nuzhat; Ahmed, Moslehuddin; Abdulrahman, Khalid Bin; D’Souza, Urban JA

2011-01-01

The rapid development of new drugs, therapies, and devices has created a dramatic increase in the number of clinical research studies that highlights the need for greater participation in research by physicians as well as patients. Furthermore, the potential of clinical research is unlikely to be reached without greater participation of physicians in research. Physicians face a variety of barriers with regard to participation in clinical research. These barriers are system-or organization-related as well as research-and physician-related. To encourage physician participation, appropriate organizational and operational infrastructures are needed in health care institutes to support research planning and management. All physicians should receive education and training in the fundamentals of research design and methodology, which need to be incorporated into undergraduate medical education and postgraduate training curricula and then reinforced through continuing medical education. Medical schools need to analyze current practices of teaching–learning and research, and reflect upon possible changes needed to develop a ‘student-focused teaching–learning and research culture’. This article examines the barriers to and benefits of physician participation in clinical research as well as interventions needed to increase their participation, including the specific role of undergraduate medical education. The main challenge is the unwillingness of many physicians and patients to participate in clinical trials. Barriers to participation include lack of time, lack of resources, trial-specific issues, communication difficulties, conflicts between the role of clinician and scientist, inadequate research experience and training for physicians, lack of rewards and recognition for physicians, and sometimes a scientifically uninteresting research question, among others. Strategies to encourage physician participation in clinical research include financial and nonfinancial incentives, adequate training, research questions that are in line with physician interests and have clear potential to improve patient care, and regular feedback. Finally, encouraging research culture and fostering the development of inquiry and research-based learning among medical students is now a high priority in order to develop more and better clinician-researchers. PMID:23745079

DianaHealth.com, an On-Line Database Containing Appraisals of the Clinical Value and Appropriateness of Healthcare Interventions: Database Development and Retrospective Analysis

PubMed Central

Bonfill, Xavier; Osorio, Dimelza; Solà, Ivan; Pijoan, Jose Ignacio; Balasso, Valentina; Quintana, Maria Jesús; Puig, Teresa; Bolibar, Ignasi; Urrútia, Gerard; Zamora, Javier; Emparanza, José Ignacio; Gómez de la Cámara, Agustín; Ferreira-González, Ignacio

2016-01-01

Objective To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database. Methods and Findings Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own. Conclusions We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice. PMID:26840451

Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium†

PubMed Central

Leon, Martin B.; Piazza, Nicolo; Nikolsky, Eugenia; Blackstone, Eugene H.; Cutlip, Donald E.; Kappetein, Arie Pieter; Krucoff, Mitchell W.; Mack, Michael; Mehran, Roxana; Miller, Craig; Morel, Marie-angèle; Petersen, John; Popma, Jeffrey J.; Takkenberg, Johanna J.M.; Vahanian, Alec; van Es, Gerrit-Anne; Vranckx, Pascal; Webb, John G.; Windecker, Stephan; Serruys, Patrick W.

2011-01-01

Objectives To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health. Background Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials. Methods and results The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended. Conclusion Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes. PMID:21216739

76 FR 52958 - Draft Guidance for Industry on Neglected Tropical Diseases of the Developing World: Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-24

...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Neglected Tropical Diseases of the Developing World: Developing Drugs for Treatment or Prevention.'' The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment or prevention of neglected diseases of the developing world. Specifically, this guidance addresses FDA's current thinking regarding the overall drug development program for the treatment or prevention of neglected tropical diseases (NTDs), including clinical trial designs and internal review standards to support approval of drugs.

Rapid Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) by the Vitek MS Saramis system.

PubMed

Shan, Weiguang; Li, Jiaping; Fang, Ying; Wang, Xuan; Gu, Danxia; Zhang, Rong

2016-01-01

A rapid, sensitive, and accurate Vitek MS assay was developed to distinguish clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) by developing an in-house knowledgebase of SuperSpectra. Three unique peaks, including peaks at 2305.6 and 3007.3 Da specific to MRSA, and 6816.7 Da specific to MSSA, were selected for differentiating MRSA and MSSA. This assay accurately identified 84 and 91% of clinical MRSA and MSSA strains out of the total 142 clinically acquired S. aureus strains that were tested. This method will greatly improve the efficiency of single clinical sample identification of MRSA, thereby facilitating a reduction in the transmission of MRSA in clinical settings.

Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities.

PubMed

Birkett, Ashley J; Moorthy, Vasee S; Loucq, Christian; Chitnis, Chetan E; Kaslow, David C

2013-04-18

While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document. Copyright © 2013 Elsevier Ltd. All rights reserved.

Conference Report: 6th Annual International Symposium on Regenerative Rehabilitation.

PubMed

Loghmani, M Terry; Roche, Joseph A

2018-04-03

The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR 3 T), included a preconference meeting of institutional representatives of the International Consortium of Regenerative Rehabilitation, keynote talks from distinguished scientists, platform and poster presentations from experts and trainees, panel discussions and postconference workshops. The following priorities were identified: increasing rigor in basic, preclinical and clinical studies, especially the use of better controls; developing better outcome measures for preclinical and clinical trials; focusing on developing more tissue-based interventions versus cell-based interventions; including regenerative rehabilitation in curricula of professional programs like occupational and physical therapy; and developing better instruments to quantify rehabilitative interventions.

Effective Strategies for Global Health Research, Training and Clinical Care: A Narrative Review

PubMed Central

Walker, Rebekah J.; Campbell, Jennifer A.; Egede, Leonard E.

2015-01-01

The purpose of this narrative review was to synthesize the evidence on effective strategies for global health research, training and clinical care in order to identify common structures that have been used to guide program development. A Medline search from 2001 to 2011 produced 951 articles, which were reviewed and categorized. Thirty articles met criteria to be included in this review. Eleven articles discussed recommendations for research, 8 discussed training and 11 discussed clinical care. Global health program development should be completed within the framework of a larger institutional commitment or partnership. Support from leadership in the university or NGO, and an engaged local community are both integral to success and sustainability of efforts. It is also important for program development to engage local partners from the onset, jointly exploring issues and developing goals and objectives. Evaluation is a recommended way to determine if goals are being met, and should include considerations of sustainability, partnership building, and capacity. Global health research programs should consider details regarding the research process, context of research, partnerships, and community relationships. Training for global health should involve mentorship, pre-departure preparation of students, and elements developed to increase impact. Clinical care programs should focus on collaboration, sustainability, meeting local needs, and appropriate process considerations. PMID:25716404

Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance.

PubMed

Mercer, Susan L; Coop, Andrew

2011-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

Predictors for delayed encephalopathy following acute carbon monoxide poisoning.

PubMed

Kudo, Kaoru; Otsuka, Kotaro; Yagi, Junko; Sanjo, Katsumi; Koizumi, Noritaka; Koeda, Atsuhiko; Umetsu, Miki Yokota; Yoshioka, Yasuhito; Mizugai, Ayumi; Mita, Toshinari; Shiga, Yu; Koizumi, Fumito; Nakamura, Hikaru; Sakai, Akio

2014-01-31

In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether "delayed neuropsychiatric sequelae (DNS)" will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases. This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc. Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions. In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks' follow-up to watch for the development of DNS is considered necessary.

Clinical Research Informatics for Big Data and Precision Medicine.

PubMed

Weng, C; Kahn, M G

2016-11-10

To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors.

Clinical Research Informatics for Big Data and Precision Medicine

PubMed Central

Kahn, M. G.

2016-01-01

Summary Objectives To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. Methods We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. Results The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. Conclusion The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors. PMID:27830253

Developing Federal Clinical Care Recommendations for Women.

PubMed

Godfrey, Emily M; Tepper, Naomi K; Curtis, Kathryn M; Moskosky, Susan B; Gavin, Loretta E

2015-08-01

The provision of family planning services has important health benefits for the U.S. Approximately 25 million women in the U.S. receive contraceptive services annually and 44 million make at least one family planning-related clinical visit each year. These services are provided by private clinicians, as well as publicly funded clinics, including specialty family planning clinics, health departments, Planned Parenthoods, community health centers, and primary care clinics. Recommendations for providing quality family planning services have been published by CDC and the Office of Population Affairs of the DHHS. This paper describes the process used to develop the women's clinical services portion of the new recommendations and the rationale underpinning them. The recommendations define family planning services as contraceptive care, pregnancy testing and counseling, achieving pregnancy, basic infertility care, sexually transmitted disease services, and preconception health. Because many women who seek family planning services have no other source of care, the recommendations also include additional screening services related to women's health, such as cervical cancer screening. These clinical guidelines are aimed at providing the highest-quality care and are designed to establish a national standard for family planning in the U.S. Published by Elsevier Inc.

Systematic review of the methodological quality of clinical guideline development for the management of chronic disease in Europe.

PubMed

Knai, Cécile; Brusamento, Serena; Legido-Quigley, Helena; Saliba, Vanessa; Panteli, Dimitra; Turk, Eva; Car, Josip; McKee, Martin; Busse, Reinhard

2012-10-01

The use of evidence-based clinical guidelines is an essential component of chronic disease management. However, there is well-documented concern about variability in the quality of clinical guidelines, with evidence of persisting methodological shortcomings. The most widely accepted approach to assessing the quality of guidelines is the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. We have conducted a systematic review of the methodological quality (as assessed by AGREE) of clinical guidelines developed in Europe for the management of chronic diseases published since 2000. The systematic review was undertaken in accordance with the Cochrane methodology. The inclusion criteria were that studies should have appraised European clinical guidelines for certain selected chronic disorders using the AGREE instrument. We searched five databases (Cab Abstracts, EMBASE, MEDLINE, Trip and EPPI). Nine studies reported in 10 papers, analysing a total of 28 European guidelines from eight countries as well as pan-European, were included. There was considerable variation in the quality of clinical guidelines across the AGREE domains. The least well addressed domains were 'editorial independence' (with a mean domain score of 41%), 'applicability' (44%), 'stakeholder involvement' (55%), and 'rigour of development' (64%), while 'clarity of presentation' (80%) and 'scope and purpose' (84%) were less problematic. This review indicates that there is considerable scope for improvement in the methods used to develop clinical guidelines for the prevention, management and treatment of chronic diseases in Europe. Given the importance of decision support strategies such as clinical guidelines in chronic disease management, improvement measures should include the explicit and transparent involvement of key stakeholders (especially scientific experts, guideline users and methodological specialists) and consideration of the implications for guideline implementation and applicability early on in the process. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Regulation of immunotherapeutic products for cancer and FDA’s role in product development and clinical evaluation

PubMed Central

2013-01-01

Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development. PMID:24764535

Development and Implementation of Sepsis Alert Systems.

PubMed

Harrison, Andrew M; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

2016-06-01

Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload, and alert fatigue, due to suboptimal alert performance. Outside the ICU, barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Current evidence does not support routine use of sepsis alert systems in clinical practice. Continuous improvement in the afferent and efferent aspects will help translate theoretic advantages into measurable patient benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

Experimental and clinical psychopharmacology: National Institute on Drug Abuse's clinical research agenda.

PubMed

Leshner, Alan I

2002-08-01

Studies of drugs and behavior are a core component of virtually every portfolio within the broad purview of the National Institute on Drug Abuse (NIDA). Moreover, psychopharmacological research is an important vehicle for advancing understanding of how drugs of abuse produce their effects, particularly including addiction. However, as with all major public health issues, simply understanding the issue is not enough. NIDA's psychopharmacology projects, therefore, span basic, clinical, and applied (e.g., medication development) research activities. These include the establishment of a nationwide clinical trials network designed to provide an infrastructure to test both behavioral and psychopharmacological treatments in a real-life practice setting with diverse patients.

Clinical development of gene- and cell-based therapies: overview of the European landscape

PubMed Central

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2016-01-01

In the last decade, many clinical trials with gene- and cell-based therapies were performed and increasing interest in the development was established by (national) authorities, academic developers, and commercial companies. However, until now only eight products have received marketing authorization (MA) approval. In this study, a comprehensive overview of the clinical development of gene- and cell-based therapies in Europe is presented, with a strong focus on product-technical aspects. Public data regarding clinical trials with gene- and cell-based therapies, obtained from the European Union (EU) clinical trial database (EudraCT) between 2004 and 2014 were analyzed, including product-technical variables as potential determinants affecting development. 198 unique gene and cell therapy products were identified, which were studied in 278 clinical trials, mostly in phase 1/2 trials and with cell therapies as major group. Furthermore, most products were manufactured from autologous starting material mostly manufactured from stem cells. The majority of the trials were sponsored by academia, whereas phase 3 trials mostly by large companies. Academia dominated early-stage development by mainly using bone marrow derived products and stem cells. Conversely, commercial sponsors were more actively pursuing in vivo gene therapy medicinal product development, and cell therapies derived from differentiated tissue in later-stage development. PMID:27990447

A review of empirical research related to the use of small quantitative samples in clinical outcome scale development.

PubMed

Houts, Carrie R; Edwards, Michael C; Wirth, R J; Deal, Linda S

2016-11-01

There has been a notable increase in the advocacy of using small-sample designs as an initial quantitative assessment of item and scale performance during the scale development process. This is particularly true in the development of clinical outcome assessments (COAs), where Rasch analysis has been advanced as an appropriate statistical tool for evaluating the developing COAs using a small sample. We review the benefits such methods are purported to offer from both a practical and statistical standpoint and detail several problematic areas, including both practical and statistical theory concerns, with respect to the use of quantitative methods, including Rasch-consistent methods, with small samples. The feasibility of obtaining accurate information and the potential negative impacts of misusing large-sample statistical methods with small samples during COA development are discussed.

Clinical leadership in pre-registration nursing programmes--an international literature review.

PubMed

Brown, Angela; Crookes, Patrick; Dewing, Jan

2015-01-01

Clinical leadership and the safety, quality and efficiency of patient/client care are inextricably linked in government reports, major inquiries and the professional literature. This review explores the literature on clinical leadership development within pre-registration nursing programmes. The literature retrieved from a scoping review was evaluated to identify what is already published on the development of clinical leadership within pre-registration nursing programmes. Twenty-seven publications matched the inclusion criteria and were included in this review, 14 journal articles, one thesis and 11 chapters within one book were analysed and three themes were identified: clinical leadership; curriculum content and pedagogy. RESULTS AND MAIN OUTCOMES: This review identified a paucity of literature specifically relating to clinical leadership and pre-registration nursing programmes and what is available is inconclusive and unconvincing. Academics, curriculum development leaders and accreditation bodies have a responsibility to influence how nurses are prepared for the profession as such clinical leadership and the new graduate should be considered an area of greater importance.

The Virtual Maternity Clinic: a teaching and learning innovation for midwifery education.

PubMed

Phillips, Diane; Duke, Maxine; Nagle, Cate; Macfarlane, Susie; Karantzas, Gery; Patterson, Denise

2013-10-01

There are challenges for midwifery students in developing skill and competency due to limited placements in antenatal clinics. The Virtual Maternity Clinic, an online resource, was developed to support student learning in professional midwifery practice. Identifying students' perceptions of the Virtual Maternity Clinic; learning about the impact of the Virtual Maternity Clinic on the students' experience of its use and access; and learning about the level of student satisfaction of the Virtual Maternity Clinic. Two interventions were used including pre and post evaluations of the online learning resource with data obtained from questionnaires using open ended and dichotomous responses and rating scales. The pre-Virtual Maternity Clinic intervention used a qualitative design and the post-Virtual Maternity Clinic intervention applied both qualitative and quantitative approaches. Three campuses of Deakin University, located in Victoria, Australia. Midwifery students enrolled in the Bachelor of Nursing/Bachelor of Midwifery and Graduate Diploma of Midwifery were recruited across three campuses of Deakin University (n=140). Thematic analysis of the pre-Virtual Maternity Clinic intervention (return rate n=119) related to students' expectations of this resource. The data for the post-Virtual Maternity Clinic intervention (return rate n=42) including open-ended responses were thematically analysed; dichotomous data examined in the form of frequencies and percentages of agreement and disagreement; and 5-rating scales were analysed using Pearson's correlations (α=.05, two-tailed). Results showed from the pre-Virtual Maternity Clinic intervention that students previously had placements in antenatal clinics were optimistic about the online learning resource. The post-Virtual Maternity Clinic intervention results indicated that students were satisfied with the Virtual Maternity Clinic as a learning resource despite some technological issues. The Virtual Maternity Clinic provides benefits for students in repeated observation of the practice of the midwife to support their professional learning and practice development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quality and efficiency successes leveraging IT and new processes.

PubMed

Chaiken, Barry P; Christian, Charles E; Johnson, Liz

2007-01-01

Today, healthcare annually invests billions of dollars in information technology, including clinical systems, electronic medical records and interoperability platforms. While continued investment and parallel development of standards are critical to secure exponential benefits from clinical information technology, intelligent and creative redesign of processes through path innovation is necessary to deliver meaningful value. Reports from two organizations included in this report review the steps taken to reinvent clinical processes that best leverage information technology to deliver safer and more efficient care. Good Samaritan Hospital, Vincennes, Indiana, implemented electronic charting, point-of-care bar coding of medications prior to administration, and integrated clinical documentation for nursing, laboratory, radiology and pharmacy. Tenet Healthcare, during its implementation and deployment of multiple clinical systems across several hospitals, focused on planning that included team-based process redesign. In addition, Tenet constructed valuable and measurable metrics that link outcomes with its strategic goals.

Evaluation of Critical Care Monitor Technology During the US Navy Strong Angel Exercise

NASA Technical Reports Server (NTRS)

Johannesen, John; Rasbury, Jack

2003-01-01

The NASA critical path road map identifies "trauma and acute medical problems" as a clinical capability risk category (http://criticalDath.isc.nasa.gov). Specific risks include major trauma, organ laceration or contusion, hemoperitoneum, pulmonary failure, pneumo- and hemothorax, burn, open bone fracture, blunt head trauma, and penetrating injury. Mitigation of these risks includes the capability for critical care monitoring. Currently, the International Space Station (ISS) Crew Health Care System (CHeCS) does not provide such a capability. The Clinical Space Medicine Strategic Planning Forum (4/8/97), sponsored by NASA Medical Operations, identified the development of trauma care capabilities as one of the top priorities for space medicine. The Clinical Care Capability Development Project (CCCDP) subsequently undertook the task to address this need.

Measuring Workload Demand of Informatics Systems with the Clinical Case Demand Index

PubMed Central

Iyengar, M. Sriram; Rogith, Deevakar; Florez-Arango, Jose F

2017-01-01

Introduction: The increasing use of Health Information Technology (HIT) can add substantially to workload on clinical providers. Current methods for assessing workload do not take into account the nature of clinical cases and the use of HIT tools while solving them. Methods: The Clinical Case Demand Index (CCDI), consisting of a summary score and visual representation, was developed to meet this need. Consistency with current perceived workload measures was evaluated in a Randomized Control Trial of a mobile health system. Results: CCDI is significantly correlated with existing workload measures and inversely related to provider performance. Discussion: CCDI combines subjective and objective characteristics of clinical cases along with cognitive and clinical dimensions. Applications include evaluation of HIT tools, clinician scheduling, medical education. Conclusion: CCDI supports comparative effectiveness research of HIT tools. In addition, CCDI could have numerous applications including training, clinical trials, design of clinical workflows, and others. PMID:29854166

Engaging Patients and Caregivers Managing Rare Diseases to Improve the Methods of Clinical Guideline Development: A Research Protocol

PubMed Central

Kinnett, Kathi; Grant, Sean; Lucas, Ann; Martin, Ann; Denger, Brian; Peay, Holly; Coulter, Ian; Fink, Arlene

2017-01-01

Background Clinical guidelines provide systematically developed recommendations for deciding on appropriate health care options for specific conditions and clinical circumstances. Up until recently, patients and caregivers have rarely been included in the process of developing care guidelines. Objective This project will develop and test a new online method for including patients and their caregivers in this process using Duchenne muscular dystrophy (DMD) care guidelines as an example. The new method will mirror and complement the RAND/UCLA Appropriateness Method (RAM)—the gold standard approach for conducting clinical expert panels that uses a modified Delphi format. RAM is often used in clinical guideline development to determine care appropriateness and necessity in situations where existing clinical evidence is uncertain, weak, or unavailable. Methods To develop the new method for engaging patients and their caregivers in guideline development, we will first conduct interviews with experts on RAM, guideline development, patient engagement, and patient-centeredness and engage with Duchenne patients and caregivers to identify how RAM should be modified for the purposes of patient engagement and what rating criteria should patients and caregivers use to provide their input during the process of guideline development. Once the new method is piloted, we will test it by conducting two concurrently run patient/caregiver panels that will rate patient-centeredness of a subset of DMD care management recommendations already deemed clinically appropriate and necessary. The ExpertLens™ system—a previously evaluated online modified Delphi system that combines two rounds of rating with a round of feedback and moderated online discussions—will be used to conduct these panels. In addition to developing and testing the new engagement method, we will work with the members of our project’s Advisory Board to generate a list of best practices for enhancing the level of patient and caregiver involvement in the guideline development process. We will solicit input on these best practice from Duchenne patients, caregivers, and clinicians by conducting a series of round-table discussions and making a presentation at an annual conference on Duchenne. Results The study protocol was reviewed by RAND’s Human Subjects Protection Committee, which determined it to be exempt from review. Interviews with RAM experts have been completed. The projected study completion date is May 2020. Conclusions We expect that the new method will make it easier to engage large numbers of patients and caregivers in the process of guideline development in a rigorous and culturally appropriate manner that is consistent with the way clinicians participate in guideline development. Moreover, this project will develop best practices that could help involve patients and caregivers in the clinical guideline development process in other clinical areas, thereby facilitating the work of guideline developers. PMID:28455279

Development of other microtubule-stabilizer families: the epothilones and their derivatives.

PubMed

Brogdon, Cynthia F; Lee, Francis Y; Canetta, Renzo M

2014-05-01

Chemotherapy is the mainstay of treatment for numerous cancer types, but resistance to chemotherapy remains a major clinical issue and is one of the driving influences underlying the development of new anticancer medications. One of the most important classes of chemotherapy agents is the taxanes, which target the cytoskeleton and spindle apparatus of tumor cells by binding to the microtubules, thereby disrupting key cellular mechanisms, including mitosis. Taxane resistance, however, limits treatment options and creates a major challenge for clinicians. Ongoing research has identified several newer classes of microtubule-targeting chemotherapies that may retain activity despite clinical resistance to taxanes. Among these classes, the epothilones have been studied most extensively in the clinical setting. Like taxanes, epothilones stabilize microtubulin turnover, and they have properties favoring their development as anticancer agents. The most clinically advanced epothilone analog is ixabepilone, which is currently the only approved epothilone derivative. Ixabepilone is indicated for the treatment of metastatic or locally advanced breast cancer in combination with capecitabine after failure of an anthracycline and a taxane, or as monotherapy after failure of an anthracycline, a taxane, and capecitabine. In phase II and III trials, ixabepilone showed efficacy in several patient subgroups and in various stages of breast cancer. Common adverse reactions include peripheral sensory neuropathy and asthenia. This paper will discuss the preclinical and clinical development of epothilones and their derivatives across a variety of cancer types.

Autism: Clinical and Research Issues.

ERIC Educational Resources Information Center

Accardo, Pasquale J., Ed.; Magnusen, Christy, Ed.; Capute, Arnold J., Ed.

This text examines the characteristics that define autism: impairments in communication; abnormal social development; and clinically significant odd behaviors. Specific chapters include: (1) Neural Mechanisms in Autism (Andrew W. Zimmerman and Barry Gordon); (2) Epidemiology of Autism and Other Pervasive Developmental Disorders: Current…

Creating ISO/EN 13606 archetypes based on clinical information needs.

PubMed

Rinner, Christoph; Kohler, Michael; Hübner-Bloder, Gudrun; Saboor, Samrend; Ammenwerth, Elske; Duftschmid, Georg

2011-01-01

Archetypes model individual EHR contents and build the basis of the dual-model approach used in the ISO/EN 13606 EHR architecture. We present an approach to create archetypes using an iterative development process. It includes automated generation of electronic case report forms from archetypes. We evaluated our approach by developing 128 archetypes which represent 446 clinical information items from the diabetes domain.

Template protocol for clinical trials investigating vaccines--focus on safety elements.

PubMed

Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2013-11-12

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective.

PubMed

McBlane, James W; Phul, Parvinder; Sharpe, Michaela

2018-06-25

This article describes preclinical development of cell-based medicinal products for European markets and discusses European regulatory mechanisms open to developers to aid successful product development. Cell-based medicinal products are diverse, including cells that are autologous or allogeneic, have been genetically modified, or not, or expanded ex vivo, and applied systemically or to an anatomical site different to that of their origin; comments applicable to one product may not be applicable to others, so bespoke development is needed, for all elements - quality, preclinical and clinical. After establishing how the product is produced, proof of potential for therapeutic efficacy, and then safety, of the product need to be determined. This includes understanding biodistribution, persistence and toxicity, including potential for malignant transformation. These elements need to be considered in the context of the intended clinical development. This article describes regulatory mechanisms available to developers to support product development that aim to resolve scientific issues prior to marketing authorization application, to enable patients to have faster access to the product than would otherwise be the case. Developers are encouraged to be aware of both the scientific issues and regulatory mechanisms to ensure patients can be supplied with these products.

Implementation of an education development project in pathology to improve student competency-lessons learnt.

PubMed

Negi, Gita; Harsh, Meena; Chauhan, Vijendra D; Kalra, Vinita; Agarwal, Pradeep; Kusum, Anuradha

2015-08-01

Basic medical sciences and clinical teachings are not coordinated in the present medical education system. They are not taught keeping in mind the outcomes required at the time of actual handling of patients in the community. An educational development project was implemented in the Department of Pathology with the aim that it will result in the student learning to link the pathophysiology of the disease to clinical scenarios and become fully competent for lifelong medical practice. The pathology teaching of the second professional batch was modified by starting with defining the desired outcomes/competencies in the student's knowledge, skills, and attitude which were then addressed by lectures, demonstrations, practical classes and small group activities where case scenarios and laboratory reports were included. The outcome was assessed by Objectively Structured Clinical/Practical Examination and multiple choice questions. Force field analysis, faculty and student interviews, and questionnaires were used to assess the factors affecting its implementation and impact. Totally 80 students of the 2(nd) Professional MBBS were exposed to a competency-based education development project. It was found that the system was appreciated by faculty and students, especially the integration with clinical scenarios. There were many factors which influenced the execution of this program, including motivation level of students and faculty, time, logistics and meticulous planning. There was a significant improvement in student's performance and satisfaction. Many factors including prior planning were a major determinant for the success of this education development project.

Opioid Analgesics and P-glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

PubMed Central

Mercer, Susan L.; Coop, Andrew

2012-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationship development to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation. PMID:21050174

An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.

PubMed

Dweik, Raed A; Boggs, Peter B; Erzurum, Serpil C; Irvin, Charles G; Leigh, Margaret W; Lundberg, Jon O; Olin, Anna-Carin; Plummer, Alan L; Taylor, D Robin

2011-09-01

Measurement of fractional nitric oxide (NO) concentration in exhaled breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While Fe(NO) measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of Fe(NO) in clinical practice. To develop evidence-based guidelines for the interpretation of Fe(NO) measurements that incorporate evidence that has accumulated over the past decade. We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. The evidence related to the use of Fe(NO) measurements is reviewed and clinical practice recommendations are provided. In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV(1) reversibility or provocation tests are only indirectly associated with airway inflammation. Fe(NO) offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy.

An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications

PubMed Central

Dweik, Raed A.; Boggs, Peter B.; Erzurum, Serpil C.; Irvin, Charles G.; Leigh, Margaret W.; Lundberg, Jon O.; Olin, Anna-Carin; Plummer, Alan L.; Taylor, D. Robin

2011-01-01

Background: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While FeNO measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of FeNO in clinical practice. Purpose: To develop evidence-based guidelines for the interpretation of FeNO measurements that incorporate evidence that has accumulated over the past decade. Methods: We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. Results: The evidence related to the use of FeNO measurements is reviewed and clinical practice recommendations are provided. Conclusions: In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV1 reversibility or provocation tests are only indirectly associated with airway inflammation. FeNO offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy. PMID:21885636

Antiviral therapeutics for the treatment of Ebola virus infection.

PubMed

Cardile, Anthony P; Downey, Lydia G; Wiseman, Perry D; Warren, Travis K; Bavari, Sina

2016-10-01

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials. We summarize relevant therapeutics that underwent clinical trials during the West Africa outbreak and highlight promising candidates under advanced development. Published by Elsevier Ltd.

Automation of CT-based haemorrhagic stroke assessment for improved clinical outcomes: study protocol and design.

PubMed

Chinda, Betty; Medvedev, George; Siu, William; Ester, Martin; Arab, Ali; Gu, Tao; Moreno, Sylvain; D'Arcy, Ryan C N; Song, Xiaowei

2018-04-19

Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors' quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging scientists, computing scientists and clinical professionals in neurology and neuroradiology and includes patient representatives. Research outputs will be disseminated following knowledge translation plans towards improving stroke patient care. Significant findings will be published in scientific journals. Anticipated deliverables include computer solutions for improved clinical assessment of haematoma using NCCT. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Validating and determining the weight of items used for evaluating clinical governance implementation based on analytic hierarchy process model.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Vafaee Najar, Ali; Meraji, Marziye; Ebrahimipour, Hossein

2015-04-08

The purpose of implementing a system such as Clinical Governance (CG) is to integrate, establish and globalize distinct policies in order to improve quality through increasing professional knowledge and the accountability of healthcare professional toward providing clinical excellence. Since CG is related to change, and change requires money and time, CG implementation has to be focused on priority areas that are in more dire need of change. The purpose of the present study was to validate and determine the significance of items used for evaluating CG implementation. The present study was descriptive-quantitative in method and design. Items used for evaluating CG implementation were first validated by the Delphi method and then compared with one another and ranked based on the Analytical Hierarchy Process (AHP) model. The items that were validated for evaluating CG implementation in Iran include performance evaluation, training and development, personnel motivation, clinical audit, clinical effectiveness, risk management, resource allocation, policies and strategies, external audit, information system management, research and development, CG structure, implementation prerequisites, the management of patients' non-medical needs, complaints and patients' participation in the treatment process. The most important items based on their degree of significance were training and development, performance evaluation, and risk management. The least important items included the management of patients' non-medical needs, patients' participation in the treatment process and research and development. The fundamental requirements of CG implementation included having an effective policy at national level, avoiding perfectionism, using the expertise and potentials of the entire country and the coordination of this model with other models of quality improvement such as accreditation and patient safety. © 2015 by Kerman University of Medical Sciences.

Challenges in evaluating clinical governance systems in iran: a qualitative study.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

2014-04-01

In spite of the pivotal role of clinical governance in enhancing quality of services provided by hospitals across the country, a scientific framework with specific criteria for evaluating hospitals has not been developed so far. This study was conducted with the aim to identify the challenges involved in evaluating systems of clinical governance in Iran. For the purposes of this qualitative study, 15 semi-structured interviews with experts in the field were conducted in 2011 and the data were analyzed using framework analysis method. Five major challenges in evaluating clinical governance include managing human resources, improving clinical quality, managing development, organizing clinical governance, and providing patient-oriented healthcare system. Healthcare system in Iran requires a clinical governance program which has a patient-oriented approach in philosophy, operation, and effectiveness in order to meet the challenges ahead.

Assessing cognitive function in clinical trials: latest developments and future directions.

PubMed

Wesnes, Keith

2002-01-01

Properly developed automated test systems are of value for assessing changes in cognitive function in clinical trials. Besides the other advantages that automation brings to trials, such as increased reliability and utility, it is shown that such systems are also more sensitive to change in cognitive function than traditional nonautomated procedures. Data from a variety of topical areas in drug development are presented to illustrate the added value such techniques have brought. The latest developments in automation include remote testing via the Internet and telephone.

Evidence-based clinical practice guideline for adult Still's disease.

PubMed

Mimura, Toshihide; Kondo, Yuya; Ohta, Akihide; Iwamoto, Masahiro; Ota, Akiko; Okamoto, Nami; Kawaguchi, Yasushi; Kono, Hajime; Takasaki, Yoshinari; Takei, Shuji; Nishimoto, Norihiro; Fujimoto, Manabu; Asanuma, Yu Funakubo; Mimori, Akio; Okiyama, Naoko; Kaneko, Shunta; Takahashi, Hiroyuki; Yokosawa, Masahiro; Sumida, Takayuki

2018-05-09

Using an expert- and data-driven methodology, we have constructed the first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after complete systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure. The CPG committee for ASD organized by the Research Team for Autoimmune Diseases, the Research Program for Intractable Disease of the Japanese Ministry of Health, Labour, and Welfare has developed CPG for ASD 2017, according to the procedure proposed by Minds. The CPG development process includes (1) clarification of the purpose of CPG, (2) organization of the steering committee, (3) organization of the CPG committee and secretariat, (4) defining the scope (setting of clinical questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the CPG, (8) external evaluation and public comments, and (9) release. Because we wanted to construct CPG for ASD to encompass both adult-onset Still's disease (AOSD) and adult patients with systemic juvenile idiopathic arthritis (sJIA), we also included SR data from sJIA in this study. Twenty-six CQs were selected and roughly divided into the following items: (1) clinical findings (CQs 1-4), (2) laboratory findings (CQs 5-8), (3) complications (CQs 9-13), (4) treatment with oral medicine (CQs 14-19), (5) treatment with biological reagents (CQs 20-23), and (6) treatments for sJIA (CQs 25-26). Recommendations and the strength of the recommendations for these CQs were decided by a modified Delphi method. We have developed the first published CPG for ASD including AOSD and sJIA, which includes 26 CQs and recommendations. This guideline will help rheumatologists, non-specialized physicians, other healthcare providers, medical and health-related students, and patients and their family members to understand and treat ASD.

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

DTIC Science & Technology

2004-08-01

will be presented at the San Antonio Breast Cancer Conference in December, 2004. The clinical data include the observation that approximately one third...of IBC patients are initially diagnosed as having mastitis and are treated with up to five months of antibiotics before the diagnosis of cancer is...developed a national registry of patients with IBC which contains standardized clinical , epidemiological and pathological information. Our registry includes

Preparing dental students for careers as independent dental professionals: clinical audit and community-based clinical teaching.

PubMed

Lynch, C D; Llewelyn, J; Ash, P J; Chadwick, B L

2011-05-28

Community-based clinical teaching programmes are now an established feature of most UK dental school training programmes. Appropriately implemented, they enhance the educational achievements and competences achieved by dental students within the earlier part of their developing careers, while helping students to traverse the often-difficult transition between dental school and vocational/foundation training and independent practice. Dental school programmes have often been criticised for 'lagging behind' developments in general dental practice - an important example being the so-called 'business of dentistry', including clinical audit. As readers will be aware, clinical audit is an essential component of UK dental practice, with the aims of improving the quality of clinical care and optimising patient safety. The aim of this paper is to highlight how training in clinical audit has been successfully embedded in the community-based clinical teaching programme at Cardiff.

Considerations for Clinical Review of Cellular Therapy Products: Perspectives of the China Food and Drug Administration Center for Drug Evaluation.

PubMed

Liu, Yantong; Zhao, Chenyang; Gao, Liucun; Yang, Huan; He, Ruyi; Gao, Chenyan

2018-02-01

With increasing numbers of technical developments and clinical studies, pioneering cellular/gene therapies are now available that could cure life-threatening disease. Cellular/gene therapy products are broad-ranging and complicated, and thereby bring challenges for clinical review by regulatory agencies. This review discusses principles for the clinical review of cellular therapy products, including protection of clinical trial populations, pharmacodynamics, pharmacokinetics, dose evaluation, clinical efficacy, clinical safety, and risk-management plans. Based on these principles, key points in the clinical review of chimeric antigen receptor T-cell therapy are also discussed.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

Design and Development of a New Multi-Projection X-Ray System for Chest Imaging

NASA Astrophysics Data System (ADS)

Chawla, Amarpreet S.; Boyce, Sarah; Washington, Lacey; McAdams, H. Page; Samei, Ehsan

2009-02-01

Overlapping anatomical structures may confound the detection of abnormal pathology, including lung nodules, in conventional single-projection chest radiography. To minimize this fundamental limiting factor, a dedicated digital multi-projection system for chest imaging was recently developed at the Radiology Department of Duke University. We are reporting the design of the multi-projection imaging system and its initial performance in an ongoing clinical trial. The system is capable of acquiring multiple full-field projections of the same patient along both the horizontal and vertical axes at variable speeds and acquisition frame rates. These images acquired in rapid succession from slightly different angles about the posterior-anterior (PA) orientation can be correlated to minimize the influence of overlying anatomy. The developed system has been tested for repeatability and motion blur artifacts to investigate its robustness for clinical trials. Excellent geometrical consistency was found in the tube motion, with positional errors for clinical settings within 1%. The effect of tube-motion on the image quality measured in terms of impact on the modulation transfer function (MTF) was found to be minimal. The system was deemed clinic-ready and a clinical trial was subsequently launched. The flexibility of image acquisition built into the system provides a unique opportunity to easily modify it for different clinical applications, including tomosynthesis, correlation imaging (CI), and stereoscopic imaging.

Experiences of undergraduate nursing students in peer assisted learning in clinical practice: a qualitative systematic review.

PubMed

Carey, Matthew C; Kent, Bridie; Latour, Jos M

2018-05-01

The objective of this qualitative systematic review was to identify and synthesize the best available evidence on experiences of peer assisted learning (PAL) among student nurses in clinical practice so as to understand the value of PAL for this population. Peer-assisted learning considers the benefits of peers working in collaboration and supporting each other in professional roles. This approach to facilitate learning is effective within universities, but there is limited exploration within the clinical practice environment. Within the UK, 50% of student nurses' learning is undertaken within clinical practice, providing a large portion of student allocation within these areas, but is unexplored in relation to PAL. Therefore, existing evidence examining PAL in clinical practice needs further exploration for a better understanding of its value to student nurses' learning. The systematic review considered studies that included male and female nursing students aged 18-50 years that explored undergraduate nursing students' experiences of PAL within the clinical practice environment. Studies that utilized designs such as phenomenology, grounded theory, ethnography, action research and feminist research were considered. Other text such as opinion papers and reports were to be considered if no qualitative studies could be located. The review excluded quantitative studies, as well as those addressing PAL outside the nursing profession and students within the nursing profession but not including undergraduate student nurses. This review considered studies that included aspects related to experiences of PAL in the clinical practice setting, as seen by undergraduate nursing students and the researcher. A three-step search strategy was undertaken to find both published and unpublished studies in English from 2003 to 2017 in various databases, and included searching of reference lists within articles selected for appraisal. Each of the included studies were assessed for methodological quality independently by two reviewers, using the Joanna Briggs Institute Critical Appraisal Form for Interpretive and Critical Research. Qualitative data was extracted using the standardized JBI qualitative data extraction tool. Qualitative research findings were synthesized using JBI methodology. From the eight included studies, 37 findings were extracted. These findings were further aggregated into seven categories, and then into three synthesized findings. These three synthesized findings are: 1) Challenges of clinical practice are mitigated by peer support; 2) Peers are role models for enhancing clinical knowledge; and 3) Support and feedback develop competence and confidence, and reduce stress and anxiety. Peer-assisted learning exists in clinical practice in both formal and informal circumstances. Friendship and community are often expressed as occurring when peers work together. Support and feedback help students develop in their clinical role and enhance clinical knowledge. Outcomes include enhancing the competency and confidence of peers, and reducing stress and anxiety. Challenges of clinical practice are mitigated through PAL.

Family Therapy in the Postmodern Era.

ERIC Educational Resources Information Center

Mills, Steven D.; Sprenkle, Douglas H.

1995-01-01

Discusses theoretical and clinical developments that have accompanied family therapy's entry into the postmodern era. Clinical trends, including use of reflecting teams, self-of-the-therapist issues, increased therapist self-disclosure, and postmodern supervision are examined. Feminist critiques, health-care reform, and increasing collaboration…

System for the Management of Trauma and Emergency Surgery in Space

NASA Technical Reports Server (NTRS)

Houtchens, B.

1984-01-01

The need to develop a systems approach to the management of trauma and other major clinical medical events in space along with appropriate development and evaluation of surgical techniques and required hardware was investigated. A prototype zero gravity surgical module was constructed and tested aboard a KC-135 aircraft during parabolic arc zero G flight. To insure parity of quality care to that available on Earth, it was recommended that a clinical medical and bioengineering advisory committee define and help develop the necessary components of the clinical medical care system for the space station and lunar base. Key components of the system are aerospace surgical training, medical equipment development, including support hardware and software, rapid access to a network of specialty expertise, and continued research and development.

Point-of-care diagnostics: extending the laboratory network to reach the last mile.

PubMed

Drain, Paul K; Rousseau, Christine

2017-03-01

More point-of-care (POC) diagnostic tests are becoming available for HIV diagnosis and treatment in resource-limited settings. These novel technologies have the potential to foster decentralized HIV care and treatment for the benefit of clinical laboratories, HIV clinics, and HIV-infected patients. There continue to be many business, technological, and operational challenges that limit product development and regulatory approval, which limits products available for the required operational and cost-effectiveness studies and delays policy adoption and implementation. Although the rapid HIV diagnostic test has been widely successful, the pathways for POC CD4 cell count and HIV viral load assay analyzers have been more challenging. We describe significant hurdles for product development, approval, and implementation, which include the business case, technical development, clinical impact, and integrating laboratory and clinical networks. The objective of this review is to highlight the obstacles for developing and implementing appropriate strategies for POC HIV testing assays to improve the clinical services for HIV-infected patients in resource-limited settings.

Detection of Intestinal Protozoa in the Clinical Laboratory

PubMed Central

McHardy, Ian H.; Wu, Max; Shimizu-Cohen, Robyn; Couturier, Marc Roger

2014-01-01

Despite recent advances in diagnostic technology, microscopic examination of stool specimens remains central to the diagnosis of most pathogenic intestinal protozoa. Microscopy is, however, labor-intensive and requires a skilled technologist. New, highly sensitive diagnostic methods have been developed for protozoa endemic to developed countries, including Giardia lamblia (syn. G. intestinalis/G. duodenalis) and Cryptosporidium spp., using technologies that, if expanded, could effectively complement or even replace microscopic approaches. To date, the scope of such novel technologies is limited and may not include common protozoa such as Dientamoeba fragilis, Entamoeba histolytica, or Cyclospora cayetanensis. This minireview describes canonical approaches for the detection of pathogenic intestinal protozoa, while highlighting recent developments and FDA-approved tools for clinical diagnosis of common intestinal protozoa. PMID:24197877

Detection of intestinal protozoa in the clinical laboratory.

PubMed

McHardy, Ian H; Wu, Max; Shimizu-Cohen, Robyn; Couturier, Marc Roger; Humphries, Romney M

2014-03-01

Despite recent advances in diagnostic technology, microscopic examination of stool specimens remains central to the diagnosis of most pathogenic intestinal protozoa. Microscopy is, however, labor-intensive and requires a skilled technologist. New, highly sensitive diagnostic methods have been developed for protozoa endemic to developed countries, including Giardia lamblia (syn. G. intestinalis/G. duodenalis) and Cryptosporidium spp., using technologies that, if expanded, could effectively complement or even replace microscopic approaches. To date, the scope of such novel technologies is limited and may not include common protozoa such as Dientamoeba fragilis, Entamoeba histolytica, or Cyclospora cayetanensis. This minireview describes canonical approaches for the detection of pathogenic intestinal protozoa, while highlighting recent developments and FDA-approved tools for clinical diagnosis of common intestinal protozoa.

Recent early clinical drug development for acute kidney injury.

PubMed

Gallagher, Kevin M; O'neill, Stephen; Harrison, Ewen M; Ross, James A; Wigmore, Stephen J; Hughes, Jeremy

2017-02-01

Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

Training oncology and palliative care clinical nurse specialists in psychological skills: evaluation of a pilot study.

PubMed

Clark, Jane E; Aitken, Susan; Watson, Nina; McVey, Joanne; Helbert, Jan; Wraith, Anita; Taylor, Vanessa; Catesby, Sarah

2015-06-01

National guidelines in the United Kingdom recommend training Clinical Nurse Specialists in psychological skills to improve the assessment and intervention with psychological problems experienced by people with a cancer diagnosis (National Institute for Health and Clinical Excellence, 2004). This pilot study evaluated a three-day training program combined with supervision sessions from Clinical Psychologists that focused on developing skills in psychological assessment and intervention for common problems experienced by people with cancer. Questionnaires were developed to measure participants' levels of confidence in 15 competencies of psychological skills. Participants completed these prior to the program and on completion of the program. Summative evaluation was undertaken and results were compared. In addition, a focus group interview provided qualitative data of participants' experiences of the structure, process, and outcomes of the program. Following the program, participants rated their confidence in psychological assessment and skills associated with providing psychological support as having increased in all areas. This included improved knowledge of psychological theories, skills in assessment and intervention and accessing and using supervision appropriately. The largest increase was in providing psycho-education to support the coping strategies of patients and carers. Thematic analysis of interview data identified two main themes including learning experiences and program enhancements. The significance of the clinical supervision sessions as key learning opportunities, achieved through the development of a community of practice, emerged. Although this pilot study has limitations, the results suggest that a combined teaching and supervision program is effective in improving Clinical Nurse Specialists' confidence level in specific psychological skills. Participants' experiences highlighted suggestions for refinement and development of the program. Opportunities for further research and developments in this area are discussed.

Drugs for rare disorders.

PubMed

Cremers, Serge; Aronson, Jeffrey K

2017-08-01

Estimates of the frequencies of rare disorders vary from country to country; the global average defined prevalence is 40 per 100 000 (0.04%). Some occur in only one or a few patients. However, collectively rare disorders are fairly common, affecting 6-8% of the US population, or about 30 million people, and a similar number in the European Union. Most of them affect children and most are genetically determined. Diagnosis can be difficult, partly because of variable presentations and partly because few clinicians have experience of individual rare disorders, although they may be assisted by searching databases. Relatively few rare disorders have specific pharmacological treatments (so-called orphan drugs), partly because of difficulties in designing trials large enough to determine benefits and harms alike. Incentives have been introduced to encourage the development of orphan drugs, including tax credits and research aids, simplification of marketing authorization procedures and exemption from fees, and extended market exclusivity. Consequently, the number of applications for orphan drugs has grown, as have the costs of using them, so much so that treatments may not be cost-effective. It has therefore been suggested that not-for-profit organizations that are socially motivated to reduce those costs should be tasked with producing them. A growing role for patient organizations, improved clinical and translational infrastructures, and developments in genetics have also contributed to successful drug development. The translational discipline of clinical pharmacology is an essential component in drug development, including orphan drugs. Clinical pharmacologists, skilled in basic pharmacology and its links to clinical medicine, can be involved at all stages. They can contribute to the delineation of genetic factors that determine clinical outcomes of pharmacological interventions, develop biomarkers, design and perform clinical trials, assist regulatory decision making, and conduct postmarketing surveillance and pharmacoepidemiological and pharmacoeconomic assessments. © 2017 The British Pharmacological Society.

Infrastructure resources for clinical research in amyotrophic lateral sclerosis.

PubMed

Sherman, Alexander V; Gubitz, Amelie K; Al-Chalabi, Ammar; Bedlack, Richard; Berry, James; Conwit, Robin; Harris, Brent T; Horton, D Kevin; Kaufmann, Petra; Leitner, Melanie L; Miller, Robert; Shefner, Jeremy; Vonsattel, Jean Paul; Mitsumoto, Hiroshi

2013-05-01

Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U.S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed.

The epidemiology of a specialist neurorehabilitation clinic: implications for clinical practice and regional service development.

PubMed

Seeley, Helen; Pickard, John; Allanson, Judith; Hutchinson, Peter

2014-01-01

To examine the epidemiology of referrals to a specialist neurotrauma clinic and explore and highlight implications for clinical practice and service development for persons with head injury/traumatic brain injury (HI/TBI). A retrospective population-based cohort study of all referrals to a specialist neurotrauma clinic over a 9-year period. Data from a specialist head injury database (which included all persons presenting to hospital with traumatic brain injury) were analysed. In total, 1235 new patients of all ages, severities of injury, both admitted and non-admitted were referred. Referrals have increased due to successful integration with new service developments and resulting optimization of resources. Data gathered from the cohort gives increased understanding of the characteristics and numbers of patients requiring rehabilitation and adds to the evidence-base. Integration with new and complementary service developments has optimized the function/aims of the clinic and enhanced its role in terms of patient service and outcome and as a research resource. The model provides principles which may be applied to planning, organizing and providing follow-up/rehabilitation services for HI/TBI.

Something has shifted: Nursing students' global perspective following international clinical placements.

PubMed

Gower, Shelley; Duggan, Ravani; Dantas, Jaya A R; Boldy, Duncan

2017-10-01

To examine understandings of global health issues among nursing students following participation in an international clinical placement during their pre-registration university education. Universities use international clinical placements, especially in developing countries, to develop cultural awareness in students; however, little is known about the longer term influences on students' understandings of global nursing. A retrospective cross-sectional design was used, using an exploratory, descriptive qualitative approach. Individual semi-structured interviews were conducted in 2014 with a purposive sample of 25 pre-registration nursing students from four Western Australian universities who undertook clinical placements across five countries. Data were analysed using inductive thematic analysis. Findings highlight that students developed new understandings around health systems including fragility of resource access, differences in clinical practice and variances in nursing roles between settings. Students also experienced challenges but were able to appreciate alternative world viewpoints. International clinical placements can develop greater awareness and help students form realistic strategies for using their nursing skills globally. Pre-placement training in cultural awareness and health system realities, along with strong supervisory support, is critical to success. © 2017 John Wiley & Sons Ltd.

Recommendations for clinical biomarker specimen preservation and stability assessments.

PubMed

Dakappagari, Naveen; Zhang, Hui; Stephen, Laurie; Amaravadi, Lakshmi; Khan, Masood U

2017-04-01

With the wide use of biomarkers to enable critical drug-development decisions, there is a growing concern from scientific community on the need for a 'standardized process' for ensuring biomarker specimen stability and hence, a strong desire to share best practices on preserving the integrity of biomarker specimens in clinical trials and the design of studies to evaluate analyte stability. By leveraging representative industry experience, we have attempted to provide an overview of critical aspects of biomarker specimen stability commonly encountered during clinical development, including: planning of clinical sample collection procedures, clinical site training, selection of sample preservation buffers, shipping logistics, fit-for-purpose stability assessments in the analytical laboratory and presentation of case studies covering widely utilized biomarker specimen types.

Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies

PubMed Central

Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

2016-01-01

Objective Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. Methods This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Results Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. Conclusion These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle weakness of sternomastoid muscle. PMID:27167831

Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies.

PubMed

Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

2016-01-01

Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle weakness of sternomastoid muscle.

Funding agencies and disease organizations: resources and recommendations to facilitate ALS clinical research.

PubMed

Chad, David A; Bidichandani, Sanjay; Bruijn, Lucie; Capra, J Donald; Dickie, Brian; Ferguson, John; Figlewicz, Denise; Forsythe, Melissa; Kaufmann, Petra; Kirshner, Annette; Monti, William

2013-05-01

Ten groups presented their perspectives on facilitating clinical research in ALS including four federal agencies, four disease organizations, one foundation and one advocacy group. The federal agencies (National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Office of Rare Diseases Research, Department of Defense) encourage fostering a team approach between pre-clinical and clinical research investigators, coordinating with patient groups in the early phases of clinical studies, enhancing private and public partnerships, and investigating the interplay between genetic susceptibility and environmental exposure. The disease organizations (Muscular Dystrophy Association, ALS Association, ALS Society of Canada, and the Motor Neurone Disease Association UK) support fellowship training programs to develop ALS clinician scientists, and encourage work on the epidemiology of ALS, on genetic and epigenetic mechanisms that are relevant to ALS pathogenesis, on developing ALS registries and biobanks, and building bridges of collaboration among study groups. The Foundation supports innovative projects, including stem-cell research, and Patient Advocacy is committed to supporting excellence in ALS research and patient care, and believes strongly in enhancing communication between patients and members of the research community.

Exploring the scope of expanding advanced nursing practice in nurse-led clinics: a multiple-case study.

PubMed

Shiu, Ann T Y; Lee, Diana T F; Chau, Janita P C

2012-08-01

This article is a report on a study to explore the development of expanding advanced nursing practice in nurse-led clinics in Hong Kong. Nurse-led clinics serviced by advanced practice nurses, a common international practice, have been adopted in Hong Kong since 1990s. Evaluations consistently show that this practice has good clinical outcomes and contributes to containing healthcare cost. However, similar to the international literature, it remains unclear as to what the elements of good advanced nursing practice are, and which directions Hong Kong should adopt for further development of such practice. A multiple-case study design was adopted with six nurse-led clinics representing three specialties as six case studies, and including two clinics each from continence, diabetes and wound care. Each case had four embedded units of analysis. They included non-participant observation of nursing activities (9 days), nurse interviews (N = 6), doctor interviews (N = 6) and client interviews (N = 12). The data were collected in 2009. Within- and cross-case analyses were conducted. The cross-case analysis demonstrated six elements of good advanced nursing practice in nurse-led clinics, and showed a great potential to expand the practice by reshaping four categories of current boundaries, including community-hospital, wellness-illness, public-private and professional-practice boundaries. From these findings, we suggest a model to advance the scope of advanced nursing practice in nurse-led clinics. The six elements may be applied as audit criteria for evaluation of advanced nursing practice in nurse-led clinics, and the proposed model provides directions for expanding such practice in Hong Kong and beyond. © 2011 Blackwell Publishing Ltd.

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics.

PubMed

Liu, Jianfang; Lichtenberg, Tara; Hoadley, Katherine A; Poisson, Laila M; Lazar, Alexander J; Cherniack, Andrew D; Kovatich, Albert J; Benz, Christopher C; Levine, Douglas A; Lee, Adrian V; Omberg, Larsson; Wolf, Denise M; Shriver, Craig D; Thorsson, Vesteinn; Hu, Hai

2018-04-05

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Copyright © 2018 Elsevier Inc. All rights reserved.

Advancing the educational and career pathway for clinical trials nurses.

PubMed

Scott, Kathleen; White, Kathryn; Roydhouse, Jessica K

2013-04-01

Clinical trials nurses play a pivotal role in the conduct of clinical research, but the educational and career pathway for these nurses remains unclear. This article reports findings from a survey of nurses working in cancer clinical trials research in Australia. Most participants held postgraduate qualifications (42 of 61); however, clinical trials education was primarily attained through short professional development courses. Interest in pursuing trial-specific postgraduate education was high, but barriers were identified, including cost, time, and unclear benefit for career advancement. Job titles varied substantially, which is indicative of an unclear employment pathway. These findings suggest that initiatives to improve the educational and career pathway for clinical trials nurses are needed and should include the following: formal educational preparation, greater consistency in employment status, and clearer career progression. These strategies should be underpinned by broad professional recognition of the clinical trials nurse as a specialized nursing role. Copyright 2013, SLACK Incorporated.

Costs of School-Located Influenza Vaccination Clinics in Maine during the 2009-2010 H1N1 Pandemic

ERIC Educational Resources Information Center

Cho, Bo-Hyun; Asay, Garrett R. Beeler; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

2012-01-01

This study retrospectively estimated costs for a convenience sample of school-located vaccination (SLV) clinics conducted in Maine during the 2009-2010 influenza season. Surveys were developed to capture the cost of labor including unpaid volunteers as well as supplies and materials used in SLV clinics. Six nurses from different school districts…

Clinical development of gene therapy: results and lessons from recent successes

PubMed Central

Kumar, Sandeep RP; Markusic, David M; Biswas, Moanaro; High, Katherine A; Herzog, Roland W

2016-01-01

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerative and metabolic disorders) and several types of cancer. Examples include restoration of vision in blind patients, eradication of blood cancers for which all other treatments had failed, correction of hemoglobinopathies and coagulation factor deficiencies, and restoration of the immune system in children born with primary immune deficiency. To date, about 2,000 clinical trials for various diseases have occurred or are in progress, and many more are in the pipeline. Multiple clinical studies reported successful treatments of pediatric patients. Design of gene therapy vectors and their clinical development are advancing rapidly. This article reviews some of the major successes in clinical gene therapy of recent years. PMID:27257611

A Methodology for Anatomic Ultrasound Image Diagnostic Quality Assessment.

PubMed

Hemmsen, Martin Christian; Lange, Theis; Brandt, Andreas Hjelm; Nielsen, Michael Bachmann; Jensen, Jorgen Arendt

2017-01-01

This paper discusses the methods for the assessment of ultrasound image quality based on our experiences with evaluating new methods for anatomic imaging. It presents a methodology to ensure a fair assessment between competing imaging methods using clinically relevant evaluations. The methodology is valuable in the continuing process of method optimization and guided development of new imaging methods. It includes a three phased study plan covering from initial prototype development to clinical assessment. Recommendations to the clinical assessment protocol, software, and statistical analysis are presented. Earlier uses of the methodology has shown that it ensures validity of the assessment, as it separates the influences between developer, investigator, and assessor once a research protocol has been established. This separation reduces confounding influences on the result from the developer to properly reveal the clinical value. This paper exemplifies the methodology using recent studies of synthetic aperture sequential beamforming tissue harmonic imaging.

Use of Developmental Milestones in Pediatric Residency Training and Practice: Time to Rethink the Meaning of the Mean

PubMed Central

Sices, Laura

2009-01-01

Objective Pediatricians frequently report the use of developmental milestones in monitoring young children’s development, despite evidence that use of screening tools improves detection of developmental delays. Methods Core texts in the field of pediatrics and developmental-behavioral pediatrics were reviewed for content and presentation on child development. Most texts included and many focused on developmental milestones, many with an emphasis on 50th percentile milestone data. Problems and limitations in the use of 50th percentile milestones to monitor young children’s development and to identify children whose development is suspicious for delay, include questionable utility in clinical decision making and the potential to increase parental anxiety. Results The recommendation is made to reconsider a focus on 50th percentile milestone data in pediatric training and practice, in favor of measures that have better clinical utility and are more psychometrically sound. Conclusion A conceptual approach to the presentation of developmental milestones differentiates the use of the 10th, 50th, and 90th percentiles of age of achievement of skills, based on the clinical purpose of surveillance. PMID:17353732

Clinical Simulation: A Protocol for Evaluation of Mobile Technology.

PubMed

Mather, Carey; Jensen, Sanne; Cummings, Elizabeth

2017-01-01

For mobile technology to be accepted at point of care in healthcare environments there is a need to demonstrate benefits whilst ameliorating the risks and challenges. To provide a standardised approach to evaluation of mobile technology a simulation protocol was developed to provide guidance for its use in healthcare environments. Simulated conditions provide the opportunity to assess intended and unintended consequences and identify potential workarounds when using technology. The protocol can also be used to demonstrate the importance of the development of digital professionalism by end-users prior to students entering the clinical practice setting. The mobile technology protocol was adapted from a health information systems protocol developed and used at the ITX Lab, Denmark for use in other simulation laboratories. Use case scenarios were developed to enable evaluation of mobile technology for mobile learning of nurses, nurse supervisors, students and patients. The scenarios can be used in a range of simulated environments including hospital bedside, outpatient clinic or community settings. A case study exemplar of a nurse and patient is included to demonstrate how the mobile technology protocol can be applied.

Emerging and recurrent issues in drug development.

PubMed

Anello, C

This paper reviews several emerging and recurrent issues relating to the drug development process. These emerging issues include changes to the FDA regulatory environment, internationalization of drug development, advances in computer technology and visualization tools, and efforts to incorporate meta-analysis methodology. Recurrent issues include: renewed interest in statistical methods for handling subgroups in the design and analysis of clinical trials; renewed interest in alternatives to the 'intention-to-treat' analysis in the presence of non-compliance in randomized clinical trials; renewed interest in methodology to address the multiplicities resulting from a variety of sources inherent in the drug development process, and renewed interest in methods to assure data integrity. These emerging and recurrent issues provide a continuing challenge to the international community of statisticians involved in drug development. Moreover, the involvement of statisticians with different perspectives continues to enrich the field and contributes to improvement in the public health.

[Status of research and development for control of tropical diseases: hypocrisy, indifference or lack of coordination].

PubMed

Millet, P

2006-12-01

Tropical diseases neglected by the pharmaceutical industry usually involve developing countries. Neglected diseases can now be divided into two groups. The first includes the big three infections i.e., malaria, HIV/AIDS, and tuberculosis, that present strategic and political overtones. The second group includes a host of other fatal infections including worms, trypanosomiasis, and leishmaniasis. Fundamental research on neglected diseases has been highly productive, but there has been little success in transferring research findings to a pharmaceutical industry unwilling to take the risks associated with developing new drugs on its own. However several public-private initiatives have revived hopes of developing new products with growing involvement of industries in developing countries (India and Brazil) despite the high risks associated with fluctuating demand for medicines or funding shortages. To meet the need for testing new drugs, more clinical facilities and better patient recruitment will be needed in endemic countries. Although these new efforts to control neglected diseases are encouraging, there is now a need for coordination. Clinical research in developing countries must be organized in compliance with international principles of ethics. Testing must be aimed at validating fundamental data from industrialized countries. Appropriate incentives must be given to ensure that pharmaceutical companies use research findings for new product development. In this context, the time seems ripe for the establishment of an independent laboratory for technological innovation in neglected diseases. Such a facility could not only validate scientific data but also supervise the development of clinical applications from research data.

Predictors for delayed encephalopathy following acute carbon monoxide poisoning

PubMed Central

2014-01-01

Background In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether “delayed neuropsychiatric sequelae (DNS)” will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases. Methods This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc. Results Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions. Conclusion In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks’ follow-up to watch for the development of DNS is considered necessary. PMID:24484081

The Assessment of Psychopathology and Behavioral Problems in Children: A Review of Scales Suitable for Epidemiological and Clinical Research (1967-1979). Mental Health Service System Reports, Series AN: Epidemiology, No. 1.

ERIC Educational Resources Information Center

Orvaschel, Helen; And Others

Forty-four scales are described that access psychopathology and/or behavior problems in children (under 18 years of age). Excluded are tests of intelligence, intellectual functioning, brain development, cognitive development, perception, and projective tests. Scales included in this review are suitable for clinical and epidemiological research,…

International collaboration including patients is essential to develop new therapies for patients with myositis.

PubMed

Lundberg, Ingrid E; Vencovsky, Jiri

2017-05-01

To discuss the needs for international collaborations between investigators in different disciplines working with myositis and with patients with myositis. Recent advances in detection of several myositis-specific autoantibodies that are associated with distinct clinical phenotypes, will enable studies in new well defined clinically homogenous subgroups of myositis This is likely to lead to development of new information on molecular pathogenesis that might be different in different myositis subgroups. Subgrouping patients according to autoantibody profile may also be important to assess outcome, to identify prognostic biomarkers and in clinical trials. As these are rare disorders international collaboration is essential to enrol large enough cohorts of the subgroups. To facilitate such collaboration we have developed a web-based international myositis register, www.euromyositis.eu, which includes validated outcome measures and patient reported outcome measures. This register is to support research but also to support decision-making in the clinic. We welcome investigators to join the Euromyositis register. Myositis is a heterogeneous disorder with varying treatment response and outcome. There is a high unmet need for new therapies which can only be achieved by increased knowledge on molecular disease mechanisms. Subgrouping patients according to autoantibody profile may be a new way forward to get a better understanding on disease mechanisms and to develop novel therapies.

Developing translational research infrastructure and capabilities associated with cancer clinical trials.

PubMed

Hall, Jacqueline A; Brown, Robert

2013-09-27

The integration of molecular information in clinical decision making is becoming a reality. These changes are shaping the way clinical research is conducted, and as reality sets in, the challenges in conducting, managing and organising multi-disciplinary research become apparent. Clinical trials provide a platform to conduct translational research (TR) within the context of high quality clinical data accrual. Integrating TR objectives in trials allows the execution of pivotal studies that provide clinical evidence for biomarker-driven treatment strategies, targeting early drug development trials to a homogeneous and well defined patient population, supports the development of companion diagnostics and provides an opportunity for deepening our understanding of cancer biology and mechanisms of drug action. To achieve these goals within a clinical trial, developing translational research infrastructure and capabilities (TRIC) plays a critical catalytic role for translating preclinical data into successful clinical research and development. TRIC represents a technical platform, dedicated resources and access to expertise promoting high quality standards, logistical and operational support and unified streamlined procedures under an appropriate governance framework. TRIC promotes integration of multiple disciplines including biobanking, laboratory analysis, molecular data, informatics, statistical analysis and dissemination of results which are all required for successful TR projects and scientific progress. Such a supporting infrastructure is absolutely essential in order to promote high quality robust research, avoid duplication and coordinate resources. Lack of such infrastructure, we would argue, is one reason for the limited effect of TR in clinical practice beyond clinical trials.

Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection

PubMed Central

Dyall, Julie; Coleman, Christopher M.; Hart, Brit J.; Venkataraman, Thiagarajan; Holbrook, Michael R.; Kindrachuk, Jason; Johnson, Reed F.; Olinger, Gene G.; Jahrling, Peter B.; Laidlaw, Monique; Johansen, Lisa M.; Lear-Rooney, Calli M.; Glass, Pamela J.; Hensley, Lisa E.

2014-01-01

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies. PMID:24841273

A Systematic Review of CPAP Adherence Across Age Groups: Clinical and Empiric Insights for Developing CPAP Adherence Interventions

PubMed Central

Sawyer, A.M.; Gooneratne, N.; Marcus, C.L.; Ofer, D.; Richards, K.C.; Weaver, T.E.

2011-01-01

Continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA) but adherence to the treatment limits its overall effectiveness across all age groups of patients. Factors that influence adherence to CPAP include disease and patient characteristics, treatment titration procedures, technological device factors and side effects, and psychological and social factors. These influential factors have guided the development of interventions to promote CPAP adherence. Various intervention strategies have been described and include educational, technological, psychosocial, pharmacological, and multi-dimensional approaches. Though evidence to date has led to innovative strategies that address adherence in CPAP-treated children, adults, and older adults, significant opportunities exist to develop and test interventions that are clinically applicable, specific to subgroups of patients likely to demonstrate poor adherence, and address the multifactorial nature of CPAP adherence. The translation of CPAP adherence promotion interventions to clinical practice is imperative to improve health and functional outcomes in all persons with CPAP-treated OSA. PMID:21652236

Development and evaluation of an electronic health record configuration and customization laboratory course for clinical informatics students.

PubMed

Mohan, Vishnu; Hersh, William R

2013-01-01

There is a need for informatics educational programs to develop laboratory courses that facilitate hands-on access to an EHR, and allow students to learn and evaluate functionality and configuration options. This is particularly relevant given the diversity of backgrounds of informatics students. We implemented an EHR laboratory course that allowed students to explore an EHR in both inpatient and outpatient clinical environments. The course focused on specific elements of the EHR including order set development, customization, clinical decision support, ancillary services, and billing and coding functionality. Students were surveyed at the end of the course for their satisfaction with the learning experience. We detailed challenges as well as lessons learned after analyzing student evaluations of this course. Features that promote the successful offering of an online EHR course, include (1) using more than one EHR to allow students to compare functionalities, (2) ensuring appropriate course calibration, (3) countering issues specific to EHR usability, and (4) fostering a fertile environment for rich online conversations are discussed.

How clinical communication has become a core part of medical education in the UK.

PubMed

Brown, Jo

2008-03-01

This paper sets out to analyse and interpret the complex events of the last 20 years in order to understand how the teaching and learning of clinical communication has emerged as a core part of the modern undergraduate medical curriculum in most medical schools in the UK. The paper analyses the effects of key political, sociological, historical and policy influences on clinical communication development. Political influences include: the effects of neo-liberalism on society and on the professions in general; the challenging of traditional notions of professionalism in medicine; the creation of an internal market within the National Health Service, and the disempowerment of the medical lobby. Sociological influences include: the effects of a 'marketised' society on medicine and subtle shifts in the doctor-patient relationship because of this; the emergence of globalised information through the Internet, and the influence of increased litigation against doctors. Historical influences include: the effects of a change in emphasis for medical education away from an inflated factual curriculum towards a curriculum that recognises the importance of student attitudes and the teaching and learning of clinical communication skills. Policy influences include the important effects of Tomorrow's Doctors and the Dearing Report on the modern medical curriculum. The paper concludes with a developmental map that charts the complex influences on clinical communication teaching and learning and a brief commentary on the growing body of teachers who deliver and develop the subject today.

Clinical development of BLZ-100 for real-time optical imaging of tumors during resection

NASA Astrophysics Data System (ADS)

Franklin, Heather L.; Miller, Dennis M.; Hedges, Teresa; Perry, Jeff; Parrish-Novak, Julia

2016-03-01

Complete initial resection can give cancer patients the best opportunity for long-term survival. There is unmet need in surgical oncology for optical imaging that enables simple and precise visualization of tumors and consistent contrast with surrounding normal tissues. Near-infrared (NIR) contrast agents and camera systems that can detect them represent an area of active research and development. The investigational Tumor Paint agent BLZ-100 is a conjugate of a chlorotoxin peptide and the NIR dye indocyanine green (ICG) that has been shown to specifically bind to a broad range of solid tumors. Clinical efficacy studies with BLZ-100 are in progress, a necessary step in bringing the product into clinical practice. To ensure a product that will be useful for and accepted by surgeons, the early clinical development of BLZ- 100 incorporates multiple tumor types and imaging devices so that surgeon feedback covers the range of anticipated clinical uses. Key contrast agent characteristics include safety, specificity, flexibility in timing between dose and surgery, and breadth of tumor types recognized. Imaging devices should use wavelengths that are optimal for the contrast agent, be sensitive enough that contrast agent dosing can be adjusted for optimal contrast, include real-time video display of fluorescence and white light image, and be simple for surgeons to use with minimal disruption of surgical flow. Rapid entry into clinical studies provides the best opportunity for early surgeon feedback, enabling development of agents and devices that will gain broad acceptance and provide information that helps surgeons achieve more complete and precise resections.

Development and psychometric testing of a Clinical Reasoning Evaluation Simulation Tool (CREST) for assessing nursing students' abilities to recognize and respond to clinical deterioration.

PubMed

Liaw, Sok Ying; Rashasegaran, Ahtherai; Wong, Lai Fun; Deneen, Christopher Charles; Cooper, Simon; Levett-Jones, Tracy; Goh, Hongli Sam; Ignacio, Jeanette

2018-03-01

The development of clinical reasoning skills in recognising and responding to clinical deterioration is essential in pre-registration nursing education. Simulation has been increasingly used by educators to develop this skill. To develop and evaluate the psychometric properties of a Clinical Reasoning Evaluation Simulation Tool (CREST) for measuring clinical reasoning skills in recognising and responding to clinical deterioration in a simulated environment. A scale development with psychometric testing and mixed methods study. Nursing students and academic staff were recruited at a university. A three-phase prospective study was conducted. Phase 1 involved the development and content validation of the CREST; Phase 2 included the psychometric testing of the tool with 15 second-year and 15 third-year nursing students who undertook the simulation-based assessment; Phase 3 involved the usability testing of the tool with nine academic staff through a survey questionnaire and focus group discussion. A 10-item CREST was developed based on a model of clinical reasoning. A content validity of 0.93 was obtained from the validation of 15 international experts. The construct validity was supported as the third-year students demonstrated significantly higher (p<0.001) clinical reasoning scores than the second-year students. The concurrent validity was also supported with significant positive correlations between global rating scores and almost all subscale scores, and the total scores. The predictive validity was supported with an existing tool. The internal consistency was high with a Cronbach's alpha of 0.92. A high inter-rater reliability was demonstrated with an intraclass correlation coefficient of 0.88. The usability of the tool was rated positively by the nurse educators but the need to ease the scoring process was highlighted. A valid and reliable tool was developed to measure the effectiveness of simulation in developing clinical reasoning skills for recognising and responding to clinical deterioration. Copyright © 2017. Published by Elsevier Ltd.

Idiopathic inflammatory myositis.

PubMed

Tieu, Joanna; Lundberg, Ingrid E; Limaye, Vidya

2016-02-01

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer.

PubMed

Parkinson, David R; McCormack, Robert T; Keating, Susan M; Gutman, Steven I; Hamilton, Stanley R; Mansfield, Elizabeth A; Piper, Margaret A; Deverka, Patricia; Frueh, Felix W; Jessup, J Milburn; McShane, Lisa M; Tunis, Sean R; Sigman, Caroline C; Kelloff, Gary J

2014-03-15

This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

Five-grass pollen immunotherapy tablet: an update on the latest findings from clinical trials: an interview with Olivier de Beaumont.

PubMed

de Beaumont, Olivier; Wilkinson, Jonathan

2014-01-01

Interview by Jonathan Wilkinson (Managing Commissioning Editor, Future Science Group). Olivier de Beaumont became Doctor of Medicine at the University of Paris Descartes in 1993. In the same year, he also took a Master of Health Economics degree at Paris Dauphine University. He is also a Master of Business Administration, ESCP Paris, 1999. At Stallergenes, he has been serving as Vice President/Head of Corporate Clinical Development since 2005, responsible for the clinical development plan, clinical operations, biometry and pharmacovigilance. In 2011, he took the responsibility of Senior Vice President Global Medical Affairs responsible for medical information and education, medical communication and nonregistration clinical studies. In 2014 he became Senior Vice President Global Scientific and Medical Affairs. From 2002 to 2005 he led the European business development of the world's leading clinical research organization Quintiles, developing Phase I-IV clinical trial programs for pharmaceutical companies. Previous roles included: Chief Scientific Officer and cofounder of Direct Medica (2000-2002), product champion and lifecycle management at Aventis (1998-2000), medical affairs manager in oncology and respiratory diseases at corporate Rhone-Poulenc Rorer (1993-1998).

Clinical anatomy e-cases: a five-year follow-up of learning analytics.

PubMed

Perumal, Vivek; Butson, Russell; Blyth, Phil; Daniel, Ben

2017-01-27

This article explores the development and user experiences of a supplementary e-learning resource (clinical anatomy e-cases) for medical students, across a five-year teaching period. A series of online supplementary e-learning resources (the clinical anatomy e-cases) were developed and introduced to the regional and clinical anatomy module of the medicine course. Usage analytics were collected online from a cohort of third-year medical students and analysed to gain a better understanding of how students utilised these resources. Key results showed that the students used the supplementary learning resource during and outside regular teaching hours that includes a significant access during holidays. Analysis also suggested that the resources were frequently accessed during examination periods and during subsequent clinical study years (fourth or fifth years of medicine course). Increasing interest and positive feedback from students has led to the development of a further series of e-cases. Tailor-made e-learning resources promote clinical anatomy learning outside classroom hours and make supplementary learning a 24/7 task.

Membrane transporters in drug development

PubMed Central

2011-01-01

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labeling. PMID:20190787

Nurse-Managed Clinics: A Blueprint for Success Using the Covey Framework.

ERIC Educational Resources Information Center

Starck, Patricia L.; And Others

1995-01-01

Describes the process from inception to successful operation of a university-based, nurse-managed clinic, based on Covey's seven habits of highly effective people. Includes information on the planning process, financing, political strategies for gaining approval, and ongoing development of services. (JOW)

Developing a Framework for Evaluating Ethical Outcomes of Good Participatory Practices in TB Clinical Drug Trials.

PubMed

MacQueen, Kathleen M; Eley, Natalie T; Frick, Mike; Mingote, Laia Ruiz; Chou, Alicia; Seidel, Stephanie S; Hannah, Stacey; Hamilton, Carol

2016-07-01

Good Participatory Practice Guidelines for TB Drug Trials (GPP-TB) were issued in 2012, based on similar guidelines for HIV prevention and reflecting growing acceptance of the importance of community engagement and participatory strategies in clinical research. Though the need for such strategies is clear, evaluation of the benefits and burdens are needed. Working with a diverse group of global TB stakeholders including advocates, scientists, and ethicists, we used a Theory of Change approach to develop an evaluation framework for GPP-TB that includes a clearly defined ethical goal, a set of powerful strategies derived from GPP-TB practices for achieving the goal, and outcomes connecting strategies to goal. The framework is a first step in systematically evaluating participatory research in clinical trials. © The Author(s) 2016.

Clinical Application of High-intensity Focused Ultrasound in Cancer Therapy

PubMed Central

Hsiao, Yi-Hsuan; Kuo, Shou-Jen; Tsai, Horng-Der; Chou, Ming-Chih; Yeh, Guang-Perng

2016-01-01

The treatment of cancer is an important issue in both developing and developed countries. Clinical use of ultrasound in cancer is not only for the diagnosis but also for the treatment. Focused ultrasound surgery (FUS) is a noninvasive technique. By using the combination of high-intensity focused ultrasound (HIFU) and imaging method, FUS has the potential to ablate tumor lesions precisely. The main mechanisms of HIFU ablation involve mechanical and thermal effects. Recent advances in HIFU have increased its popularity. Some promising results were achieved in managing various malignancies, including pancreas, prostate, liver, kidney, breast and bone. Other applications include brain tumor ablation and disruption of the blood-brain barrier. We aim at briefly outlining the clinical utility of FUS as a noninvasive technique for a variety of types of cancer treatment. PMID:26918034

Ceramics in Restorative and Prosthetic DENTISTRY1

NASA Astrophysics Data System (ADS)

Kelly, J. Robert

1997-08-01

This review is intended to provide the ceramic engineer with information about the history and current use of ceramics in dentistry, contemporary research topics, and potential research agenda. Background material includes intra-oral design considerations, descriptions of ceramic dental components, and the origin, composition, and microstructure of current dental ceramics. Attention is paid to efforts involving net-shape processing, machining as a forming method, and the analysis of clinical failure. A rationale is presented for the further development of all-ceramic restorative systems. Current research topics receiving attention include microstructure/processing/property relationships, clinical failure mechanisms and in vitro testing, wear damage and wear testing, surface treatments, and microstructural modifications. The status of the field is critically reviewed with an eye toward future work. Significant improvements seem possible in the clinical use of ceramics based on engineering solutions derived from the study of clinically failed restorations, on the incorporation of higher levels of "biomimicry" in new systems, and on the synergistic developments in dental cements and adhesive dentin bonding.

A Decade of Development of Chromogenic Culture Media for Clinical Microbiology in an Era of Molecular Diagnostics.

PubMed

Perry, John D

2017-04-01

In the last 25 years, chromogenic culture media have found widespread application in diagnostic clinical microbiology. In the last decade, the range of media available to clinical laboratories has expanded greatly, allowing specific detection of additional pathogens, including Pseudomonas aeruginosa, group B streptococci, Clostridium difficile, Campylobacter spp., and Yersinia enterocolitica. New media have also been developed to screen for pathogens with acquired antimicrobial resistance, including vancomycin-resistant enterococci, carbapenem-resistant Acinetobacter spp., and Enterobacteriaceae with extended-spectrum β-lactamases and carbapenemases. This review seeks to explore the utility of chromogenic media in clinical microbiology, with particular attention given to media that have been commercialized in the last decade. The impact of laboratory automation and complementary technologies such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is also assessed. Finally, the review also seeks to demarcate the role of chromogenic media in an era of molecular diagnostics. © Crown copyright 2017.

A risk-management approach for effective integration of biomarkers in clinical trials: perspectives of an NCI, NCRI, and EORTC working group.

PubMed

Hall, Jacqueline Anne; Salgado, Roberto; Lively, Tracy; Sweep, Fred; Schuh, Anna

2014-04-01

Clinical cancer research today often includes testing the value of biomarkers to direct treatment and for drug development. However, the practical challenges of integration of molecular information into clinical trial protocols are increasingly appreciated. Inherent difficulties include evidence gaps in available biomarker data, a paucity of robust assay methods, and the design of appropriate studies within the constraints of feasible trial operations, and finite resources. Scalable and proportionate approaches are needed to systematically cope with these challenges. Therefore, we assembled international experts from three clinical trials organisations to identify the common challenges and common solutions. We present a practical risk-assessment framework allowing targeting of scarce resources to crucial issues coupled with a library of useful resources and a simple actionable checklist of recommendations. We hope that these practical methods will be useful for running biomarker-driven trials and ultimately help to develop biomarkers that are ready for integration in routine practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Decade of Development of Chromogenic Culture Media for Clinical Microbiology in an Era of Molecular Diagnostics

PubMed Central

2017-01-01

SUMMARY In the last 25 years, chromogenic culture media have found widespread application in diagnostic clinical microbiology. In the last decade, the range of media available to clinical laboratories has expanded greatly, allowing specific detection of additional pathogens, including Pseudomonas aeruginosa, group B streptococci, Clostridium difficile, Campylobacter spp., and Yersinia enterocolitica. New media have also been developed to screen for pathogens with acquired antimicrobial resistance, including vancomycin-resistant enterococci, carbapenem-resistant Acinetobacter spp., and Enterobacteriaceae with extended-spectrum β-lactamases and carbapenemases. This review seeks to explore the utility of chromogenic media in clinical microbiology, with particular attention given to media that have been commercialized in the last decade. The impact of laboratory automation and complementary technologies such as matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is also assessed. Finally, the review also seeks to demarcate the role of chromogenic media in an era of molecular diagnostics. PMID:28122803

[Melasma : An update on the clinical picture, treatment, and prevention].

PubMed

Becker, S; Schiekofer, C; Vogt, T; Reichrath, J

2017-02-01

Melasma, also known as chloasma or mask of pregnancy, presents clinically as hyperpigmented skin areas, which develop mostly in the face as a consequence of increased synthesis of melanin. The established treatment options, including topically applied agents and the use of various laser systems, mostly result in improvement but not in complete remission of the lesions. Because of its significant impact on quality of life and the limited effectivity of available treatment options, the management of melasma is challenging for the treating physician. Although many risk factors, including pregnancy and UV exposure, have been identified, the pathogenesis is not yet fully understood. Avoiding solar or artificial UV exposure is of high importance both for the prevention of melasma and for the clinical outcome of existing lesions. In order to avoid vitamin D deficiency, oral vitamin D supplementation should be recommended. In this review, we give an update on clinical aspects, epidemiology, pathogenesis and therapy of melasma and give an outlook on future developments.

How can we improve clinical research in pneumonia?

PubMed

Ramirez, Julio A

2018-05-01

The primary challenges in the field of clinical research include a lack of support within existing infrastructure, insufficient number of clinical research training programs and a paucity of qualified mentors. Most medical centers offer infrastructure support for investigators working with industry sponsors or government-funded clinical trials, yet there are a significant amount of clinical studies performed in the field of pneumonia which are observational studies. For this type of research, which is frequently unfunded, support is usually lacking. In an attempt to optimize clinical research in pneumonia, at the University of Louisville, we developed a clinical research coordinating center (CRCC). The center manages clinical studies in the field of respiratory infections, with the primary focus being pneumonia. Other activities of the CRCC include the organization of an annual clinical research training course for physicians and other healthcare workers, and the facilitation of international research mentoring by a process of connecting new pneumonia investigators with established clinical investigators. To improve clinical research in pneumonia, institutions need to have the appropriate infrastructure in place to support investigators in all aspects of the clinical research process.

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists.

PubMed

Boycott, Kym; Hartley, Taila; Adam, Shelin; Bernier, Francois; Chong, Karen; Fernandez, Bridget A; Friedman, Jan M; Geraghty, Michael T; Hume, Stacey; Knoppers, Bartha M; Laberge, Anne-Marie; Majewski, Jacek; Mendoza-Londono, Roberto; Meyn, M Stephen; Michaud, Jacques L; Nelson, Tanya N; Richer, Julie; Sadikovic, Bekim; Skidmore, David L; Stockley, Tracy; Taylor, Sherry; van Karnebeek, Clara; Zawati, Ma'n H; Lauzon, Julie; Armour, Christine M

2015-07-01

The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Transforming community services through the use of a multidimensional model of clinical leadership.

PubMed

Leigh, Jacqueline Anne; Wild, Jill; Hynes, Celia; Wells, Stuart; Kurien, Anish; Rutherford, June; Rosen, Lyn; Ashcroft, Tim; Hartley, Victoria

2015-03-01

To evaluate the application of a Multidimensional Model of Clinical Leadership on the community healthcare leader and on transforming community services. Healthcare policy advocates clinical leadership as the vehicle to transform community and healthcare services. Few studies have identified the key components of an effective clinical leadership development model. The first two stages of Kirkpatrick's (Personnel Administrator 28, 1983, 62) Four/Five Levels of Evaluation were used to evaluate the application of the multidimensional model of clinical leadership. Eighty community healthcare leaders were exposed to this multidimensional clinical leadership development model through attendance of a community clinical leadership development programme. Twenty five leaders participated in focus group interviews. Data from the interviews were analysed utilising thematic content analysis. Three key themes emerged that influenced the development of best practice principles for clinical leadership development: 1. Personal leadership development 2. Organisational leadership 3. The importance of multiprofessional action learning/reflective groups Emergent best practice principles for clinical leadership development include adopting a multidimensional development approach. This approach encompasses: preparing the individual leader in the role and seeking organisational leadership development that promotes the vision and corporate values of the organisation and delivers on service improvement and innovation. Moreover, application of the Multidimensional Model of Clinical Leadership could offer the best platform for embedding the Six C's of Nursing (Compassion in Practice - Our Culture of Compassionate Care, Department of Health, Crown Copyright, 2012) within the culture of the healthcare organisation: care, compassion, courage, commitment, communication, and competency. This is achieved in part through the application of emotional intelligence to understand self and to develop the personal integrity of the healthcare leader and through supporting a culture of lifelong leadership learning. Embedding the best practice principles of clinical leadership development within a multidimensional model of clinical leadership provides a promising approach to: equipping the healthcare leader with those transferable leadership skills required to help them embark on a journey of lifelong leadership learning; and producing the healthcare leader who is caring, compassionate and can confidently and effectively transform community services. © 2014 John Wiley & Sons Ltd.

Evolution of an information literacy curriculum for third-year medical students.

PubMed

O'Dwyer, Linda; Kerns, Stephanie C

2011-01-01

Information literacy curriculum for third-year medical students at Northwestern University has evolved over several years under the guidance of librarians at the Galter Health Sciences Library. Starting as a series of rotation-specific information resource overviews, initial evaluation and feedback led to the curriculum being developed to include more focused and interactive clinical information sessions with a quiz-based assessment. Future enhancements will include web-based self-directed learning using online tutorials, additional search exercises that mimic the on-the-go clinical environment, and better assessment of the curriculum's impact on students' information literacy and clinical search skills.

Developing prehospital clinical practice guidelines for resource limited settings: why re-invent the wheel?

PubMed

McCaul, Michael; de Waal, Ben; Hodkinson, Peter; Pigoga, Jennifer L; Young, Taryn; Wallis, Lee A

2018-02-05

Methods on developing new (de novo) clinical practice guidelines (CPGs) have received substantial attention. However, the volume of literature is not matched by research into alternative methods of CPG development using existing CPG documents-a specific issue for guideline development groups in low- and middle-income countries. We report on how we developed a context specific prehospital CPG using an alternative guideline development method. Difficulties experienced and lessons learnt in applying existing global guidelines' recommendations to a national context are highlighted. The project produced the first emergency care CPG for prehospital providers in Africa. It included > 270 CPGs and produced over 1000 recommendations for prehospital emergency care. We encountered various difficulties, including (1) applicability issues: few pre-hospital CPGs applicable to Africa, (2) evidence synthesis: heterogeneous levels of evidence classifications and (3) guideline quality. Learning points included (1) focusing on key CPGs and evidence mapping, (2) searching other resources for CPGs, (3) broad representation on CPG advisory boards and (4) transparency and knowledge translation. Re-inventing the wheel to produce CPGs is not always feasible. We hope this paper will encourage further projects to use existing CPGs in developing guidance to improve patient care in resource-limited settings.

Implementation issues relevant to outpatient neurology palliative care.

PubMed

Kluger, Benzi M; Persenaire, Michael J; Holden, Samantha K; Palmer, Laura T; Redwine, Hannah; Berk, Julie; Anderson, C Alan; Filley, Christopher M; Kutner, Jean; Miyasaki, Janis; Carter, Julie

2017-11-29

There is growing interest in the application of palliative care principles to improve care for patients and families affected by neurologic diseases. We developed an interdisciplinary outpatient clinic for patients and families affected by neurologic disorders to better address the problems faced by our highest need patients. We have developed and improved this program over the past three years and share several of our most important lessons as well as ongoing challenges and areas where we see our clinic evolving in the future. We provide a description of our clinic logistics, including key steps in the initiation of the clinic, and provide descriptions from similar clinics at other institutions to demonstrate some of the variability in this growing field. We also provide results from a formal one-year quality improvement project and a one-year retrospective study of patients attending this clinic. Our clinic has grown steadily since its inception and maintains high satisfaction ratings from patients, caregivers, and referring providers. To maintain standardized and efficient care we have developed materials for patients and referring physicians as well as checklists and other processes used by our interdisciplinary team. Feedback from our quality improvement project helped define optimal visit duration and refine communication among team members and with patients and families. Results from our chart review suggest our clinic influences advance care planning and place of death. Common referral reasons include psychosocial support, complex symptom management, and advance care planning. Current challenges for our clinic include developing a strategy for continued growth, creating a sustainable financial model for interdisciplinary care, integrating our services with disease-specific sections, improving primary palliative care knowledge and skills within our referral base, and building effective alliances with community neurologists, geriatrics, primary care, nursing homes, and hospices. Specialized outpatient palliative care for neurologic disorders fills several important gaps in care for this patient population, provides important educational opportunities for trainees, and creates opportunities for patient and caregiver-centered research. Educational initiatives are needed to train general neurologists in primary palliative care, to train neurologists in specialist palliative care, and to train palliative medicine specialists in neurology. Research is needed to build an evidence base to identify patient and caregiver needs, support specific interventions, and to build more efficient models of care in both academic and community settings.

Clinical pathologist in Korea--training program and its roles in laboratories.

PubMed

Cho, Han-Ik; Lee, Kap No; Park, Jong-Woo; Park, Hyosoon; Kwak, Yun Sik

2002-01-01

A rapid development of practice of laboratory medicine in Korea owes its success to the clinical pathologists (CP), who have played a role of a pathfinder for laboratories. The Korean CP postgraduate education (residency) program is unique in that it is exclusively for laboratory medicine. The training program for clinical pathologists includes diagnostic hematology, diagnostic immunology, clinical microbiology, clinical chemistry, blood bank, diagnostic genetics, informatics and laboratory management. The program has produced a strong group of about 600 laboratory physicians, officially clinical pathologists since 1963. Most of Korean clinical pathologists work as laboratory directors, directors of university hospital laboratories or teaching faculty members in medical schools. The roles of clinical pathologists are laboratory management, interpretation of laboratory test results, clinical consulting services to clinicians and patients, ordering secondary tests after reviews of requested test results and utilization management. The clinical pathologists have developed clinical laboratories to be a main contributor for improved medical practice. During the last 40 years under the turbulent healthcare system, clinical pathologists have significantly contributed to safeguard the laboratory interests. The education program and the role of clinical pathologists are described.

Framework for development of physician competencies in genomic medicine: report of the Competencies Working Group of the Inter-Society Coordinating Committee for Physician Education in Genomics.

PubMed

Korf, Bruce R; Berry, Anna B; Limson, Melvin; Marian, Ali J; Murray, Michael F; O'Rourke, P Pearl; Passamani, Eugene R; Relling, Mary V; Tooker, John; Tsongalis, Gregory J; Rodriguez, Laura L

2014-11-01

Completion of the Human Genome Project, in conjunction with dramatic reductions in the cost of DNA sequencing and advances in translational research, is gradually ushering genomic discoveries and technologies into the practice of medicine. The rapid pace of these advances is opening up a gap between the knowledge available about the clinical relevance of genomic information and the ability of clinicians to include such information in their medical practices. This educational gap threatens to be rate limiting to the clinical adoption of genomics in medicine. Solutions will require not only a better understanding of the clinical implications of genetic discoveries but also training in genomics at all levels of professional development, including for individuals in formal training and others who long ago completed such training. The National Human Genome Research Institute has convened the Inter-Society Coordinating Committee for Physician Education in Genomics (ISCC) to develop and share best practices in the use of genomics in medicine. The ISCC has developed a framework for development of genomics practice competencies that may serve as a starting point for formulation of competencies for physicians in various medical disciplines.

Status of vaccine research and development of vaccines for herpes simplex virus.

PubMed

Johnston, Christine; Gottlieb, Sami L; Wald, Anna

2016-06-03

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Clinical case definition for the diagnosis of acute intussusception.

PubMed

Bines, Julie E; Ivanoff, Bernard; Justice, Frances; Mulholland, Kim

2004-11-01

Because of the reported association between intussusception and a rotavirus vaccine, future clinical trials of rotavirus vaccines will need to include intussusception surveillance in the evaluation of vaccine safety. The aim of this study is to develop and validate a clinical case definition for the diagnosis of acute intussusception. A clinical case definition for the diagnosis of acute intussusception was developed by analysis of an extensive literature review that defined the clinical presentation of intussusception in 70 developed and developing countries. The clinical case definition was then assessed for sensitivity and specificity using a retrospective chart review of hospital admissions. Sensitivity of the clinical case definition was assessed in children diagnosed with intussusception over a 6.5-year period. Specificity was assessed in patients aged <2 years admitted with bowel obstruction and in patients aged <19 years presenting with symptoms that may occur in intussusception. The clinical case definition accurately identified 185 of 191 assessable cases as "probable" intussusception and six cases as "possible" intussusception (sensitivity, 97%). No case of radiologic or surgically proven intussusception failed to be identified by the clinical case definition. The specificity of the definition in correctly identifying patients who did not have intussusception ranged from 87% to 91%. The clinical case definition for intussusception may assist in the prompt identification of patients with intussusception and may provide an important tool for the future trials of enteric vaccines.

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

PubMed

Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

Language Development, Delay and Intervention--The Views of Parents from Communities That Speech and Language Therapy Managers in England Consider to Be Under-Served

ERIC Educational Resources Information Center

Marshall, Julie; Harding, Sam; Roulstone, Sue

2017-01-01

Background: Evidence-based practice includes research evidence, clinical expertise and stakeholder perspectives. Stakeholder perspectives are important and include parental ethno-theories, which embrace views about many aspects of speech, language and communication, language development, and interventions. The Developmental Niche Framework…

Mild cognitive impairment: historical development and summary of research

PubMed Central

Golomb, James; Kluger, Alan; Ferris, Steven H

2004-01-01

This review article broadly traces the historical development, diagnostic criteria, clinical and neuropathological characteristics, and treatment strategies related to mild cognitive impairment (MCI), The concept of MCI is considered in the context of other terms that have been developed to characterize the elderly with varying degrees of cognitive impairment Criteria based on clinical global scale ratings, cognitive test performance, and performance on other domains of functioning are discussed. Approaches employing clinical, neuropsychological, neuroimaging, biological, and molecular genetic methodology used in the validation of MCI are considered, including results from cross-sectional, longitudinal, and postmortem investigations. Results of recent drug treatment studies of MCI and related methodological issues are also addressed. PMID:22034453

Challenges in Evaluating Clinical Governance Systems in Iran: A Qualitative Study

PubMed Central

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

2014-01-01

Background: In spite of the pivotal role of clinical governance in enhancing quality of services provided by hospitals across the country, a scientific framework with specific criteria for evaluating hospitals has not been developed so far. Objectives: This study was conducted with the aim to identify the challenges involved in evaluating systems of clinical governance in Iran. Materials and Methods: For the purposes of this qualitative study, 15 semi-structured interviews with experts in the field were conducted in 2011 and the data were analyzed using framework analysis method. Results: Five major challenges in evaluating clinical governance include managing human resources, improving clinical quality, managing development, organizing clinical governance, and providing patient-oriented healthcare system. Conclusions: Healthcare system in Iran requires a clinical governance program which has a patient-oriented approach in philosophy, operation, and effectiveness in order to meet the challenges ahead. PMID:24910799

Replication of clinical innovations in multiple medical practices.

PubMed

Henley, N S; Pearce, J; Phillips, L A; Weir, S

1998-11-01

Many clinical innovations had been successfully developed and piloted in individual medical practice units of Kaiser Permanente in North Carolina during 1995 and 1996. Difficulty in replicating these clinical innovations consistently throughout all 21 medical practice units led to development of the interdisciplinary Clinical Innovation Implementation Team, which was formed by using existing resources from various departments across the region. REPLICATION MODEL: Based on a model of transfer of best practices, the implementation team developed a process and tools (master schedule and activity matrix) to quickly replicate successful pilot projects throughout all medical practice units. The process involved the following steps: identifying a practice and delineating its characteristics and measures (source identification); identifying a team to receive the (new) practice; piloting the practice; and standardizing, including the incorporation of learnings. The model includes the following components for each innovation: sending and receiving teams, an innovation coordinator role, an innovation expert role, a location expert role, a master schedule, and a project activity matrix. Communication depended on a partnership among the location experts (local knowledge and credibility), the innovation coordinator (process expertise), and the innovation experts (content expertise). Results after 12 months of working with the 21 medical practice units include integration of diabetes care team services into the practices, training of more than 120 providers in the use of personal computers and an icon-based clinical information system, and integration of a planwide self-care program into the medical practices--all with measurable improved outcomes. The model for sequential replication and the implementation team structure and function should be successful in other organizational settings.

Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products.

PubMed

Nicolette, C A; Healey, D; Tcherepanova, I; Whelton, P; Monesmith, T; Coombs, L; Finke, L H; Whiteside, T; Miesowicz, F

2007-09-27

Dendritic cell (DC) active immunotherapy is potentially efficacious in a broad array of malignant disease settings. However, challenges remain in optimizing DC-based therapy for maximum clinical efficacy within manufacturing processes that permit quality control and scale-up of consistent products. In this review we discuss the critical issues that must be addressed in order to optimize DC-based product design and manufacture, and highlight the DC based platforms currently addressing these issues. Variables in DC-based product design include the type of antigenic payload used, DC maturation steps and activation processes, and functional assays. Issues to consider in development include: (a) minimizing the invasiveness of patient biological material collection; (b) minimizing handling and manipulations of tissue at the clinical site; (c) centralized product manufacturing and standardized processing and capacity for commercial-scale production; (d) rapid product release turnaround time; (e) the ability to manufacture sufficient product from limited starting material; and (f) standardized release criteria for DC phenotype and function. Improvements in the design and manufacture of DC products have resulted in a handful of promising leads currently in clinical development.

Blending technology in teaching advanced health assessment in a family nurse practitioner program: using personal digital assistants in a simulation laboratory.

PubMed

Elliott, Lydia; DeCristofaro, Claire; Carpenter, Alesia

2012-09-01

This article describes the development and implementation of integrated use of personal handheld devices (personal digital assistants, PDAs) and high-fidelity simulation in an advanced health assessment course in a graduate family nurse practitioner (NP) program. A teaching tool was developed that can be utilized as a template for clinical case scenarios blending these separate technologies. Review of the evidence-based literature, including peer-reviewed articles and reviews. Blending the technologies of high-fidelity simulation and handheld devices (PDAs) provided a positive learning experience for graduate NP students in a teaching laboratory setting. Combining both technologies in clinical case scenarios offered a more real-world learning experience, with a focus on point-of-care service and integration of interview and physical assessment skills with existing standards of care and external clinical resources. Faculty modeling and advance training with PDA technology was crucial to success. Faculty developed a general template tool and systems-based clinical scenarios integrating PDA and high-fidelity simulation. Faculty observations, the general template tool, and one scenario example are included in this article. ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.

Chiropractic quality assurance: standards and guidelines

PubMed Central

Gatterman, Meridel I; Dobson, Thomas P; LeFevbre, Ron

2001-01-01

Chiropractic quality assurance involves development of both clinical guidelines and standards. Confusion generated by poor differentiation of guidelines from standards contributes to mistrust of the guideline development process. Guidelines are considered to be recommendations that allow for flexibility and individual patient differences. Standards are more binding and require a high level of supporting evidence. While guidelines serve as educational tools to improve the quality of practice, standards that outline minimum competency are used more as administrative tools on which to base policy. Barriers to development of clinical guidelines and standards include fear that they will create prescriptive “cookbook” practice, and the distrust that guidelines are developed primarily for cost containment. Clinicians also criticize guidelines developed by academics that don't relate to practice, and those based on evidence that lacks clinical relevance. Conflicting guidelines perceived to be based on strong bias or conflict of interest are also suspect. To reduce barriers to acceptance and implementation, guidelines should be inclusive, patient-centered, and based on a variety of evidence and clinical experience.

Biomedical research, development, and engineering at the Johns Hopkins University Applied Physics Laboratory. Annual report 1 October 1978-30 September 1979

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The Medical Institutions of The Johns Hopkins University and The Johns Hopkins University Applied Physics Laboratory have developed a vigorous collaborative program of biomedical research, development, and systems engineering. An important objective of the program is to apply the expertise in engineering, the physical sciences, and systems analysis acquired by APL in defense and space research and development to problems of medical research and health care delivery. This program has grown to include collaboration with many of the clinical and basic science departments of the medical divisions. Active collaborative projects exist in ophthalmology, neurosensory research and instrumentation development, cardiovascular systems,more » patient monitoring, therapeutic and rehabilitation systems, clinical information systems, and clinical engineering. This application of state-of-the-art technology has contributed to advances in many areas of basic medical research and in clinical diagnosis and therapy through improvement of instrumentation, techniques, and basic understanding.« less

Developing a point-of-care electronic medical record system for TB/HIV co-infected patients: experiences from Lighthouse Trust, Lilongwe, Malawi.

PubMed

Tweya, Hannock; Feldacker, Caryl; Gadabu, Oliver Jintha; Ng'ambi, Wingston; Mumba, Soyapi L; Phiri, Dave; Kamvazina, Luke; Mwakilama, Shawo; Kanyerere, Henry; Keiser, Olivia; Mwafilaso, Johnbosco; Kamba, Chancy; Egger, Matthias; Jahn, Andreas; Simwaka, Bertha; Phiri, Sam

2016-03-05

Implementation of user-friendly, real-time, electronic medical records for patient management may lead to improved adherence to clinical guidelines and improved quality of patient care. We detail the systematic, iterative process that implementation partners, Lighthouse clinic and Baobab Health Trust, employed to develop and implement a point-of-care electronic medical records system in an integrated, public clinic in Malawi that serves HIV-infected and tuberculosis (TB) patients. Baobab Health Trust, the system developers, conducted a series of technical and clinical meetings with Lighthouse and Ministry of Health to determine specifications. Multiple pre-testing sessions assessed patient flow, question clarity, information sequencing, and verified compliance to national guidelines. Final components of the TB/HIV electronic medical records system include: patient demographics; anthropometric measurements; laboratory samples and results; HIV testing; WHO clinical staging; TB diagnosis; family planning; clinical review; and drug dispensing. Our experience suggests that an electronic medical records system can improve patient management, enhance integration of TB/HIV services, and improve provider decision-making. However, despite sufficient funding and motivation, several challenges delayed system launch including: expansion of system components to include of HIV testing and counseling services; changes in the national antiretroviral treatment guidelines that required system revision; and low confidence to use the system among new healthcare workers. To ensure a more robust and agile system that met all stakeholder and user needs, our electronic medical records launch was delayed more than a year. Open communication with stakeholders, careful consideration of ongoing provider input, and a well-functioning, backup, paper-based TB registry helped ensure successful implementation and sustainability of the system. Additional, on-site, technical support provided reassurance and swift problem-solving during the extended launch period. Even when system users are closely involved in the design and development of an electronic medical record system, it is critical to allow sufficient time for software development, solicitation of detailed feedback from both users and stakeholders, and iterative system revisions to successfully transition from paper to point-of-care electronic medical records. For those in low-resource settings, electronic medical records for integrated care is a possible and positive innovation.

Model-Based Approach to Predict Adherence to Protocol During Antiobesity Trials.

PubMed

Sharma, Vishnu D; Combes, François P; Vakilynejad, Majid; Lahu, Gezim; Lesko, Lawrence J; Trame, Mirjam N

2018-02-01

Development of antiobesity drugs is continuously challenged by high dropout rates during clinical trials. The objective was to develop a population pharmacodynamic model that describes the temporal changes in body weight, considering disease progression, lifestyle intervention, and drug effects. Markov modeling (MM) was applied for quantification and characterization of responder and nonresponder as key drivers of dropout rates, to ultimately support the clinical trial simulations and the outcome in terms of trial adherence. Subjects (n = 4591) from 6 Contrave ® trials were included in this analysis. An indirect-response model developed by van Wart et al was used as a starting point. Inclusion of drug effect was dose driven using a population dose- and time-dependent pharmacodynamic (DTPD) model. Additionally, a population-pharmacokinetic parameter- and data (PPPD)-driven model was developed using the final DTPD model structure and final parameter estimates from a previously developed population pharmacokinetic model based on available Contrave ® pharmacokinetic concentrations. Last, MM was developed to predict transition rate probabilities among responder, nonresponder, and dropout states driven by the pharmacodynamic effect resulting from the DTPD or PPPD model. Covariates included in the models and parameters were diabetes mellitus and race. The linked DTPD-MM and PPPD-MM was able to predict transition rates among responder, nonresponder, and dropout states well. The analysis concluded that body-weight change is an important factor influencing dropout rates, and the MM depicted that overall a DTPD model-driven approach provides a reasonable prediction of clinical trial outcome probabilities similar to a pharmacokinetic-driven approach. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer.

PubMed

Subramaniam, Deepa; He, Aiwu Ruth; Hwang, Jimmy; Deeken, John; Pishvaian, Michael; Hartley, Marion L; Marshall, John L

2015-01-01

Overactivation of the ErbB protein family, which is comprised of 4 receptor tyrosine kinase members (ErbB1/epidermal growth factor receptor [EGFR]/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4), can drive the development and progression of a wide variety of malignancies, including colorectal, head and neck, and certain non-small cell lung cancers (NSCLCs). As a result, agents that target a specific member of the ErbB family have been developed for the treatment of cancer. These agents include the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib; the EGFR-targeting monoclonal antibodies cetuximab and panitumumab; and the HER2-targeting monoclonal antibody trastuzumab. Lapatinib is a dual TKI that targets both EGFR and HER2. In addition, TKIs that inhibit multiple members of the ErbB family and also bind their targets irreversibly are under evaluation for the treatment of cancer. Three such compounds have progressed into clinical studies: the EGFR, HER2, and HER4 inhibitors afatinib, dacomitinib, and neratinib. Phase I studies of these agents have shown clinical activity in NSCLC, breast cancer, and other malignancies. Currently, afatinib is approved for EGFR mutation-positive NSCLC and is in development for squamous NSCLC, and dacomitinib is in phase III of clinical development for NSCLC, neratinib is in phase III of clinical development for the treatment of breast cancer, and afatinib is also in phase III development in head and neck cancer. Final results from clinical trials may lead to the potential approval of these agents in a variety of solid tumor malignancies.

National Institute of Neurological Disorders and Stroke Common Data Element Project - approach and methods.

PubMed

Grinnon, Stacie T; Miller, Kristy; Marler, John R; Lu, Yun; Stout, Alexandra; Odenkirchen, Joanne; Kunitz, Selma

2012-06-01

In neuroscience clinical research studies, much time and effort are devoted to deciding what data to collect and developing data collection forms and data management systems to capture the data. Many investigators receiving funding from National Institute of Neurological Disorders and Stroke (NINDS), the National Institutes of Health (NIH), are required to share their data once their studies are complete, but the multitude of data definitions and formats make it extremely difficult to aggregate data or perform meta-analyses across studies. In an effort to assist investigators and accelerate data sharing in neuroscience clinical research, the NINDS has embarked upon the Common Data Element (CDE) Project. The data standards developed through the NINDS CDE Project enable clinical investigators to systematically collect data and should facilitate study start-up and data aggregation across the research community. The NINDS CDE Team has taken a systematic, iterative approach to develop the critical core and the disease-specific CDEs. The CDE development process provides a mechanism for community involvement and buy-in, offers a structure for decision making, and includes a technical support team. Upon conclusion of the development process, the CDEs and accompanying tools are available on the Project Web site - http://www.commondataelements.ninds.nih.gov/. The Web site currently includes the critical core (aka general) CDEs that are applicable to all clinical research studies regardless of therapeutic area as well as several disease-specific CDEs. Additional disease-specific CDEs will be added to the Web site once they are developed and vetted over the next 12 months. The CDEs will continue to evolve and will improve only if clinical researchers use and offer feedback about their experience with them. Thus, the NINDS program staff strongly encourages its clinical research grantees to use the CDEs and is expanding its efforts to educate the neuroscience research community about the CDEs and to train research teams to incorporate them into their studies. Version 1.0 of a set of CDEs has been published, but publication is not the end of the development process. All CDEs will be evaluated and revised at least annually to ensure that they reflect current clinical research practices in neuroscience.

An academic-health service partnership in nursing: lessons from the field.

PubMed

Granger, Bradi B; Prvu-Bettger, Janet; Aucoin, Julia; Fuchs, Mary Ann; Mitchell, Pamela H; Holditch-Davis, Diane; Roth, Deborah; Califf, Robert M; Gilliss, Catherine L

2012-03-01

To describe the development of an academic-health services partnership undertaken to improve use of evidence in clinical practice. Academic health science schools and health service settings share common elements of their missions: to educate, participate in research, and excel in healthcare delivery, but differences in the business models, incentives, and approaches to problem solving can lead to differences in priorities. Thus, academic and health service settings do not naturally align their leadership structures or work processes. We established a common commitment to accelerate the appropriate use of evidence in clinical practice and created an organizational structure to optimize opportunities for partnering that would leverage shared resources to achieve our goal. A jointly governed and funded institute integrated existing activities from the academic and service sectors. Additional resources included clinical staff and student training and mentoring, a pilot research grant-funding program, and support to access existing data. Emergent developments include an appreciation for a wider range of investigative methodologies and cross-disciplinary teams with skills to integrate research in daily practice and improve patient outcomes. By developing an integrated leadership structure and commitment to shared goals, we developed a framework for integrating academic and health service resources, leveraging additional resources, and forming a mutually beneficial partnership to improve clinical outcomes for patients. Structurally integrated academic-health service partnerships result in improved evidence-based patient care delivery and in a stronger foundation for generating new clinical knowledge, thus improving patient outcomes. © 2012 Sigma Theta Tau International.

Describing and Modeling Workflow and Information Flow in Chronic Disease Care

PubMed Central

Unertl, Kim M.; Weinger, Matthew B.; Johnson, Kevin B.; Lorenzi, Nancy M.

2009-01-01

Objectives The goal of the study was to develop an in-depth understanding of work practices, workflow, and information flow in chronic disease care, to facilitate development of context-appropriate informatics tools. Design The study was conducted over a 10-month period in three ambulatory clinics providing chronic disease care. The authors iteratively collected data using direct observation and semi-structured interviews. Measurements The authors observed all aspects of care in three different chronic disease clinics for over 150 hours, including 157 patient-provider interactions. Observation focused on interactions among people, processes, and technology. Observation data were analyzed through an open coding approach. The authors then developed models of workflow and information flow using Hierarchical Task Analysis and Soft Systems Methodology. The authors also conducted nine semi-structured interviews to confirm and refine the models. Results The study had three primary outcomes: models of workflow for each clinic, models of information flow for each clinic, and an in-depth description of work practices and the role of health information technology (HIT) in the clinics. The authors identified gaps between the existing HIT functionality and the needs of chronic disease providers. Conclusions In response to the analysis of workflow and information flow, the authors developed ten guidelines for design of HIT to support chronic disease care, including recommendations to pursue modular approaches to design that would support disease-specific needs. The study demonstrates the importance of evaluating workflow and information flow in HIT design and implementation. PMID:19717802

Progress and challenges in viral vector manufacturing

PubMed Central

van der Loo, Johannes C.M.; Wright, J. Fraser

2016-01-01

Promising results in several clinical studies have emphasized the potential of gene therapy to address important medical needs and initiated a surge of investments in drug development and commercialization. This enthusiasm is driven by positive data in clinical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency, Leber's Congenital Amaurosis Type 2 and in cancer immunotherapy trials for hematological malignancies using chimeric antigen receptor T cells. These results build on the recent licensure of the European gene therapy product Glybera for the treatment of lipoprotein lipase deficiency. The progress from clinical development towards product licensure of several programs presents challenges to gene therapy product manufacturing. These include challenges in viral vector-manufacturing capacity, where an estimated 1–2 orders of magnitude increase will likely be needed to support eventual commercial supply requirements for many of the promising disease indications. In addition, the expanding potential commercial product pipeline and the continuously advancing development of recombinant viral vectors for gene therapy require that products are well characterized and consistently manufactured to rigorous tolerances of purity, potency and safety. Finally, there is an increase in regulatory scrutiny that affects manufacturers of investigational drugs for early-phase clinical trials engaged in industry partnerships. Along with the recent increase in biopharmaceutical funding in gene therapy, industry partners are requiring their academic counterparts to meet higher levels of GMP compliance at earlier stages of clinical development. This chapter provides a brief overview of current progress in the field and discusses challenges in vector manufacturing. PMID:26519140

Clinical skills development in student-run free clinic volunteers: a multi-trait, multi-measure study.

PubMed

Nakamura, Mio; Altshuler, David; Chadwell, Margit; Binienda, Juliann

2014-12-12

At Wayne State University School of Medicine (WSU SOM), the Robert R. Frank Student Run Free Clinic (SRFC) is one place preclinical students can gain clinical experience. There have been no published studies to date measuring the impact of student-run free clinic (SRFC) volunteerism on clinical skills development in preclinical medical students. Surveys were given to first year medical students at WSU SOM at the beginning and end of Year 1 to assess perception of clinical skills, including self-confidence, self-reflection, and professionalism. Scores of the Year 1 Objective Structured Clinical Exam (OSCE) were compared between SRFC volunteers and non-volunteers. There were a total of 206 (68.2%) and 80 (26.5%) survey responses at the beginning and end of Year 1, respectively. Of the 80 students, 31 (38.7%) volunteered at SRFC during Year 1. Statistically significant differences were found between time points in self-confidence (p < 0.001) in both groups. When looking at self-confidence in skills pertaining to SRFC, the difference between groups was statistically significant (p = 0.032) at both time points. A total of 302 students participated in the Year 1 OSCE, 27 (9%) of which were SRFC volunteers. No statistically significant differences were found between groups for mean score (p = 0.888) and established level of rapport (p = 0.394). While this study indicated no significant differences in clinical skills in students who volunteer at the SRFC, it is a first step in attempting to measure clinical skill development outside of the structured medical school setting. The findings lend themselves to development of research designs, clinical surveys, and future studies to measure the impact of clinical volunteer opportunities on clinical skills development in future physicians.

Behavioral Medicine Training in Postdoctoral Dental Education.

ERIC Educational Resources Information Center

Lockhart, Peter B.; And Others

1992-01-01

Carolinas Medical Center (North Carolina) initiated a behavioral training program for general practice dental residents to develop skills in handling patient anxiety/stress, obesity, and depression. The program includes monthly seminars, a clinical rotation in behavioral medicine with additional related seminars, and a month-long clinical rotation…

Clinical Linguistics--Retrospect and Prospect.

ERIC Educational Resources Information Center

Grunwell, Pamela

In the past 20 years, linguistics has gained a prominent position in speech and language pathology in Britain, evolving into a new field, clinical linguistics. It includes three related areas of activity: training of speech pathologists/therapists; professional practice; and research. Linguistics and speech/language pathology have developed as…

The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials.

PubMed

Welch, Mary Jane; Lally, Rachel; Miller, Jennifer E; Pittman, Stephanie; Brodsky, Lynda; Caplan, Arthur L; Uhlenbrauck, Gina; Louzao, Darcy M; Fischer, James H; Wilfond, Benjamin

2015-10-01

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. © The Author(s) 2015.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research

PubMed Central

McCann, Liza J; Pilkington, Clarissa A; Huber, Adam M; Ravelli, Angelo; Appelbe, Duncan; Kirkham, Jamie J; Williamson, Paula R; Aggarwal, Amita; Christopher-Stine, Lisa; Constantin, Tamas; Feldman, Brian M; Lundberg, Ingrid; Maillard, Sue; Mathiesen, Pernille; Murphy, Ruth; Pachman, Lauren M; Reed, Ann M; Rider, Lisa G; van Royen-Kerkof, Annet; Russo, Ricardo; Spinty, Stefan; Wedderburn, Lucy R

2018-01-01

Objectives This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres. Methods A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation. Results A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter. Conclusions Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases. PMID:29084729

Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

PubMed

Doody, R

2017-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

Development of a clinical prediction model to calculate patient life expectancy: the measure of actuarial life expectancy (MALE).

PubMed

Clarke, M G; Kennedy, K P; MacDonagh, R P

2009-01-01

To develop a clinical prediction model enabling the calculation of an individual patient's life expectancy (LE) and survival probability based on age, sex, and comorbidity for use in the joint decision-making process regarding medical treatment. A computer software program was developed with a team of 3 clinicians, 2 professional actuaries, and 2 professional computer programmers. This incorporated statistical spreadsheet and database access design methods. Data sources included life insurance industry actuarial rating factor tables (public and private domain), Government Actuary Department UK life tables, professional actuarial sources, and evidence-based medical literature. The main outcome measures were numerical and graphical display of comorbidity-adjusted LE; 5-, 10-, and 15-year survival probability; in addition to generic UK population LE. Nineteen medical conditions, which impacted significantly on LE in actuarial terms and were commonly encountered in clinical practice, were incorporated in the final model. Numerical and graphical representations of statistical predictions of LE and survival probability were successfully generated for patients with either no comorbidity or a combination of the 19 medical conditions included. Validation and testing, including actuarial peer review, confirmed consistency with the data sources utilized. The evidence-based actuarial data utilized in this computer program design represent a valuable resource for use in the clinical decision-making process, where an accurate objective assessment of patient LE can so often make the difference between patients being offered or denied medical and surgical treatment. Ongoing development to incorporate additional comorbidities and enable Web-based access will enhance its use further.

Designing and Evaluating an Interactive Multimedia Web-Based Simulation for Developing Nurses’ Competencies in Acute Nursing Care: Randomized Controlled Trial

PubMed Central

Wong, Lai Fun; Chan, Sally Wai-Chi; Ho, Jasmine Tze Yin; Mordiffi, Siti Zubaidah; Ang, Sophia Bee Leng; Goh, Poh Sun; Ang, Emily Neo Kim

2015-01-01

Background Web-based learning is becoming an increasingly important instructional tool in nursing education. Multimedia advancements offer the potential for creating authentic nursing activities for developing nursing competency in clinical practice. Objective This study aims to describe the design, development, and evaluation of an interactive multimedia Web-based simulation for developing nurses’ competencies in acute nursing care. Methods Authentic nursing activities were developed in a Web-based simulation using a variety of instructional strategies including animation video, multimedia instructional material, virtual patients, and online quizzes. A randomized controlled study was conducted on 67 registered nurses who were recruited from the general ward units of an acute care tertiary hospital. Following a baseline evaluation of all participants’ clinical performance in a simulated clinical setting, the experimental group received 3 hours of Web-based simulation and completed a survey to evaluate their perceptions of the program. All participants were re-tested for their clinical performances using a validated tool. Results The clinical performance posttest scores of the experimental group improved significantly (P<.001) from the pretest scores after the Web-based simulation. In addition, compared to the control group, the experimental group had significantly higher clinical performance posttest scores (P<.001) after controlling the pretest scores. The participants from the experimental group were satisfied with their learning experience and gave positive ratings for the quality of the Web-based simulation. Themes emerging from the comments about the most valuable aspects of the Web-based simulation include relevance to practice, instructional strategies, and fostering problem solving. Conclusions Engaging in authentic nursing activities using interactive multimedia Web-based simulation can enhance nurses’ competencies in acute care. Web-based simulations provide a promising educational tool in institutions where large groups of nurses need to be trained in acute nursing care and accessibility to repetitive training is essential for achieving long-term retention of clinical competency. PMID:25583029

Designing and evaluating an interactive multimedia Web-based simulation for developing nurses' competencies in acute nursing care: randomized controlled trial.

PubMed

Liaw, Sok Ying; Wong, Lai Fun; Chan, Sally Wai-Chi; Ho, Jasmine Tze Yin; Mordiffi, Siti Zubaidah; Ang, Sophia Bee Leng; Goh, Poh Sun; Ang, Emily Neo Kim

2015-01-12

Web-based learning is becoming an increasingly important instructional tool in nursing education. Multimedia advancements offer the potential for creating authentic nursing activities for developing nursing competency in clinical practice. This study aims to describe the design, development, and evaluation of an interactive multimedia Web-based simulation for developing nurses' competencies in acute nursing care. Authentic nursing activities were developed in a Web-based simulation using a variety of instructional strategies including animation video, multimedia instructional material, virtual patients, and online quizzes. A randomized controlled study was conducted on 67 registered nurses who were recruited from the general ward units of an acute care tertiary hospital. Following a baseline evaluation of all participants' clinical performance in a simulated clinical setting, the experimental group received 3 hours of Web-based simulation and completed a survey to evaluate their perceptions of the program. All participants were re-tested for their clinical performances using a validated tool. The clinical performance posttest scores of the experimental group improved significantly (P<.001) from the pretest scores after the Web-based simulation. In addition, compared to the control group, the experimental group had significantly higher clinical performance posttest scores (P<.001) after controlling the pretest scores. The participants from the experimental group were satisfied with their learning experience and gave positive ratings for the quality of the Web-based simulation. Themes emerging from the comments about the most valuable aspects of the Web-based simulation include relevance to practice, instructional strategies, and fostering problem solving. Engaging in authentic nursing activities using interactive multimedia Web-based simulation can enhance nurses' competencies in acute care. Web-based simulations provide a promising educational tool in institutions where large groups of nurses need to be trained in acute nursing care and accessibility to repetitive training is essential for achieving long-term retention of clinical competency.

The Idaho dedicated education unit model: cost-effective, high-quality education.

PubMed

Springer, Pamela J; Johnson, Patricia; Lind, Bonnie; Walker, Eldon; Clavelle, Joanne; Jensen, Nancy

2012-01-01

Faculty face many challenges in delivering clinical education, including faculty availability, the complexity of the faculty role, and limited clinical placements. Dedicated education units (DEUs) are being explored as alternatives to traditional clinical placement models. The authors describe the successful development of a DEU that resulted in positive student outcomes at reduced cost to both the school and the medical center.

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

PubMed Central

Miller, Paul E.; Mannis, Mark J.

2015-01-01

Abstract This article reviews ocular adverse events (AEs) reported in association with administration of antibody–drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID:26539624

New antibiotics for healthcare-associated pneumonia.

PubMed

Neuner, Elizabeth A; Ritchie, David J; Micek, Scott T

2009-02-01

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

Emergence of a scientific and commercial research and development infrastructure for human gene therapy.

PubMed

Crofts, Christine; Krimsky, Sheldon

2005-02-01

A research and clinical subfield known as "human gene therapy" has grown rapidly since 1990, when the first human trials were approved in the United States. Using quantitative data, this paper describes and analyzes the research and commercial infrastructure, including academic centers, publications, intellectual property, and biotechnology firms, that has developed around the goal of discovering clinical applications for the modification and transport of DNA to somatic cells. Despite setbacks and few documented successes, the subfield of human gene therapy continues to serve as an influential clinical paradigm for the treatment of inherited and noninherited diseases.

Incorporation of Novel MRI and Biomarkers into Prostate Cancer Active Surveillance Risk Assessment

DTIC Science & Technology

2017-09-01

preparation for a career in clinical research. These goals include 1) training in T1 translational research; 2) training in the development and...clinical trials network). In addition to basic mentoring tasks, we have identified four sources of mentorship in particular to my career , which...to meet the goals of my grant and career development. Research: We have successfully implemented the acquisition portion of the RSI MRI. There

Summary and Recommendations from the National Cancer Institute’s Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

PubMed Central

Lerner, Seth P.; Bajorin, Dean F.; Dinney, Colin P.; Efstathiou, Jason A.; Groshen, Susan; Hahn, Noah M.; Hansel, Donna; Kwiatkowski, David; O’Donnell, Michael; Rosenberg, Jonathan; Svatek, Robert; Abrams, Jeffrey S.; Al-Ahmadie, Hikmat; Apolo, Andrea B.; Bellmunt, Joaquim; Callahan, Margaret; Cha, Eugene K.; Drake, Charles; Jarow, Jonathan; Kamat, Ashish; Kim, William; Knowles, Margaret; Mann, Bhupinder; Marchionni, Luigi; McConkey, David; McShane, Lisa; Ramirez, Nilsa; Sharabi, Andrew; Sharpe, Arlene H.; Solit, David; Tangen, Catherine M.; Amiri, Abdul Tawab; Van Allen, Eliezer; West, Pamela J.; Witjes, J. A.; Quale, Diane Zipursky

2016-01-01

The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure). PMID:27376138

Recent development of transcatheter closure of atrial septal defect and patent foramen ovale with occluders.

PubMed

Tang, Baiyu; Su, Feng; Sun, Xiangke; Wu, Qin; Xing, Quansheng; Li, Suming

2018-01-01

Atrial septal defect (ASD) and patent foramen ovale (PFO) are common clinical congenital heart defects. As an effective method for the treatment of ASD and PFO, transcatheter closure with occluders presents many advantages, including safety, ease of operation, minimal invasiveness, and reduced complications. This contribution reviews the various types of occluders currently used in clinical applications and under development, including non degradable occluders, partially degradable occluders, and totally degradable occluders. A number of case studies are described in detail. Comparison is made on the treatment outcomes using different occulders. Future development of transcatheter closure is discussed, in particular the use of totally degradable occluders. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 433-443, 2018. © 2016 Wiley Periodicals, Inc.

Engineering Delivery Vehicles for Genome Editing.

PubMed

Nelson, Christopher E; Gersbach, Charles A

2016-06-07

The field of genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by genome editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for genome editing are reviewed, and promising advances in particular therapeutic applications are discussed.

45 CFR Appendix A to Part 1355 - Foster Care Data Elements

Code of Federal Regulations, 2011 CFR

2011-10-01

... Abuse (Child)—Child's compulsive use of or need for alcohol. This element should include infants... include infants addicted at birth. Child's Disability—Clinical diagnosis by a qualified professional of..., growth, and moral development. These may include adjudicated or nonadjudicated child behavior problems...

45 CFR Appendix A to Part 1355 - Foster Care Data Elements

Code of Federal Regulations, 2010 CFR

2010-10-01

... Abuse (Child)—Child's compulsive use of or need for alcohol. This element should include infants... include infants addicted at birth. Child's Disability—Clinical diagnosis by a qualified professional of..., growth, and moral development. These may include adjudicated or nonadjudicated child behavior problems...

Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks.

PubMed

Tsukamoto, Katusra; Carroll, Kelly A; Onishi, Taku; Matsumaru, Naoki; Brasseur, Daniel; Nakamura, Hidefumi

2016-03-01

A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (<18 years old) between 2006 and 2014. Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P < 0.001) and 0.066 (P = 0.498), respectively. Those between Japan and the United States were 0.560 (P < 0.001) and 0.281 (P = 0.002), indicating that pediatric drug development in Japan was more active after the introduction of these premiums, even reaching the level of the European Union. The Pediatric Regulation and the Paediatric Committee promoted pediatric drug development in the European Union. The registered number of clinical trials that includes at least 1 participants <18 years old in the European Union Clinical Trials Register increased by 247 trials (from 672) in the 1000 days after regulation. The ratio of pediatric clinical trials with an approved Paediatric Investigation Plan increased to >15% after 2008. Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and community. Expanding the regulatory steps taken in the European Union, United States, and Japan and using innovative clinical trial tools can move pediatric pharmacotherapy out of its current therapeutic orphan state. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Validation of Immunohistochemical Assays for Integral Biomarkers in the NCI-MATCH EAY131 Clinical Trial.

PubMed

Khoury, Joseph D; Wang, Wei-Lien; Prieto, Victor G; Medeiros, L Jeffrey; Kalhor, Neda; Hameed, Meera; Broaddus, Russell; Hamilton, Stanley R

2018-02-01

Biomarkers that guide therapy selection are gaining unprecedented importance as targeted therapy options increase in scope and complexity. In conjunction with high-throughput molecular techniques, therapy-guiding biomarker assays based upon immunohistochemistry (IHC) have a critical role in cancer care in that they inform about the expression status of a protein target. Here, we describe the validation procedures for four clinical IHC biomarker assays-PTEN, RB, MLH1, and MSH2-for use as integral biomarkers in the nationwide NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) EAY131 clinical trial. Validation procedures were developed through an iterative process based on collective experience and adaptation of broad guidelines from the FDA. The steps included primary antibody selection; assay optimization; development of assay interpretation criteria incorporating biological considerations; and expected staining patterns, including indeterminate results, orthogonal validation, and tissue validation. Following assay lockdown, patient samples and cell lines were used for analytic and clinical validation. The assays were then approved as laboratory-developed tests and used for clinical trial decisions for treatment selection. Calculations of sensitivity and specificity were undertaken using various definitions of gold-standard references, and external validation was required for the PTEN IHC assay. In conclusion, validation of IHC biomarker assays critical for guiding therapy in clinical trials is feasible using comprehensive preanalytic, analytic, and postanalytic steps. Implementation of standardized guidelines provides a useful framework for validating IHC biomarker assays that allow for reproducibility across institutions for routine clinical use. Clin Cancer Res; 24(3); 521-31. ©2017 AACR . ©2017 American Association for Cancer Research.

'Cloud computing' and clinical trials: report from an ECRIN workshop.

PubMed

Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques

2015-07-29

Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies.

Improving clinical trials for cardiovascular diseases: a position paper from the Cardiovascular Round Table of the European Society of Cardiology.

PubMed

Jackson, Neville; Atar, Dan; Borentain, Maria; Breithardt, Günter; van Eickels, Martin; Endres, Matthias; Fraass, Uwe; Friede, Tim; Hannachi, Hakima; Janmohamed, Salim; Kreuzer, Jörg; Landray, Martin; Lautsch, Dominik; Le Floch, Chantal; Mol, Peter; Naci, Huseyin; Samani, Nilesh J; Svensson, Anders; Thorstensen, Cathrine; Tijssen, Jan; Vandzhura, Victoria; Zalewski, Andrew; Kirchhof, Paulus

2016-03-01

Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines. The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development. A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

From Systems Understanding to Personalized Medicine: Lessons and Recommendations Based on a Multidisciplinary and Translational Analysis of COPD.

PubMed

Roca, Josep; Cano, Isaac; Gomez-Cabrero, David; Tegnér, Jesper

2016-01-01

Systems medicine, using and adapting methods and approaches as developed within systems biology, promises to be essential in ongoing efforts of realizing and implementing personalized medicine in clinical practice and research. Here we review and critically assess these opportunities and challenges using our work on COPD as a case study. We find that there are significant unresolved biomedical challenges in how to unravel complex multifactorial components in disease initiation and progression producing different clinical phenotypes. Yet, while such a systems understanding of COPD is necessary, there are other auxiliary challenges that need to be addressed in concert with a systems analysis of COPD. These include information and communication technology (ICT)-related issues such as data harmonization, systematic handling of knowledge, computational modeling, and importantly their translation and support of clinical practice. For example, clinical decision-support systems need a seamless integration with new models and knowledge as systems analysis of COPD continues to develop. Our experience with clinical implementation of systems medicine targeting COPD highlights the need for a change of management including design of appropriate business models and adoption of ICT providing and supporting organizational interoperability among professional teams across healthcare tiers, working around the patient. In conclusion, in our hands the scope and efforts of systems medicine need to concurrently consider these aspects of clinical implementation, which inherently drives the selection of the most relevant and urgent issues and methods that need further development in a systems analysis of disease.

Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

PubMed

Abbasalizadeh, Saeed; Baharvand, Hossein

2013-12-01

Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

A multimedia electronic patient record (ePR) system for image-assisted minimally invasive spinal surgery.

PubMed

Documet, Jorge; Le, Anh; Liu, Brent; Chiu, John; Huang, H K

2010-05-01

This paper presents the concept of bridging the gap between diagnostic images and image-assisted surgical treatment through the development of a one-stop multimedia electronic patient record (ePR) system that manages and distributes the real-time multimodality imaging and informatics data that assists the surgeon during all clinical phases of the operation from planning Intra-Op to post-care follow-up. We present the concept of this multimedia ePR for surgery by first focusing on image-assisted minimally invasive spinal surgery as a clinical application. Three clinical phases of minimally invasive spinal surgery workflow in Pre-Op, Intra-Op, and Post-Op are discussed. The ePR architecture was developed based on the three-phased workflow, which includes the Pre-Op, Intra-Op, and Post-Op modules and four components comprising of the input integration unit, fault-tolerant gateway server, fault-tolerant ePR server, and the visualization and display. A prototype was built and deployed to a minimally invasive spinal surgery clinical site with user training and support for daily use. A step-by-step approach was introduced to develop a multimedia ePR system for imaging-assisted minimally invasive spinal surgery that includes images, clinical forms, waveforms, and textual data for planning the surgery, two real-time imaging techniques (digital fluoroscopic, DF) and endoscope video images (Endo), and more than half a dozen live vital signs of the patient during surgery. Clinical implementation experiences and challenges were also discussed.

Enhancing decision making about participation in cancer clinical trials: development of a question prompt list

PubMed Central

Brown, Richard F.; Shuk, Elyse; Leighl, Natasha; Butow, Phyllis; Ostroff, Jamie; Edgerson, Shawna; Tattersall, Martin

2016-01-01

Purpose Slow accrual to cancer clinical trials impedes the progress of effective new cancer treatments. Poor physician–patient communication has been identified as a key contributor to low trial accrual. Question prompt lists (QPLs) have demonstrated a significant promise in facilitating communication in general, surgical, and palliative oncology settings. These simple patient interventions have not been tested in the oncology clinical trial setting. We aimed to develop a targeted QPL for clinical trials (QPL-CT). Method Lung, breast, and prostate cancer patients who either had (trial experienced) or had not (trial naive) participated in a clinical trial were invited to join focus groups to help develop and explore the acceptability of a QPL-CT. Focus groups were audio-recorded and transcribed. A research team, including a qualitative data expert, analyzed these data to explore patients’ decision-making processes and views about the utility of the QPL-CT prompt to aid in trial decision making. Results Decision making was influenced by the outcome of patients’ comparative assessment of perceived risks versus benefits of a trial, and the level of trust patients had in their doctors’ recommendation about the trial. Severity of a patient’s disease influenced trial decision making only for trial-naive patients. Conclusion Although patients were likely to prefer a paternalistic decision-making style, they expressed valuation of the QPL as an aid to decision making. QPL-CT utility extended beyond the actual consultation to include roles both before and after the clinical trial discussion. PMID:20593202

Advances in Basic and Clinical Immunology 2009

PubMed Central

Chinen, Javier; Shearer, William T.

2010-01-01

In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1INH concentrate in hereditary angioedema patients demonstrated the safety of its use and the efficacy to reduce duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports establishing the significant role of toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced over 15 new genetic defects related to the immune response, including DOCK8 mutations responsible for the autosomal recessive form of the hyper IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia and myelokathexis (WHIM) syndrome, or the occurrence of mucormycosis and Serratia infections in chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in humoral immunodeficiencies was recognized and recommendations for management were reviewed. Clinical research focused in severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when diagnosis is made early before opportunistic infections occur. PMID:20226292

Clinical Bioinformatics: challenges and opportunities

PubMed Central

2012-01-01

Background Network Tools and Applications in Biology (NETTAB) Workshops are a series of meetings focused on the most promising and innovative ICT tools and to their usefulness in Bioinformatics. The NETTAB 2011 workshop, held in Pavia, Italy, in October 2011 was aimed at presenting some of the most relevant methods, tools and infrastructures that are nowadays available for Clinical Bioinformatics (CBI), the research field that deals with clinical applications of bioinformatics. Methods In this editorial, the viewpoints and opinions of three world CBI leaders, who have been invited to participate in a panel discussion of the NETTAB workshop on the next challenges and future opportunities of this field, are reported. These include the development of data warehouses and ICT infrastructures for data sharing, the definition of standards for sharing phenotypic data and the implementation of novel tools to implement efficient search computing solutions. Results Some of the most important design features of a CBI-ICT infrastructure are presented, including data warehousing, modularity and flexibility, open-source development, semantic interoperability, integrated search and retrieval of -omics information. Conclusions Clinical Bioinformatics goals are ambitious. Many factors, including the availability of high-throughput "-omics" technologies and equipment, the widespread availability of clinical data warehouses and the noteworthy increase in data storage and computational power of the most recent ICT systems, justify research and efforts in this domain, which promises to be a crucial leveraging factor for biomedical research. PMID:23095472

Electrophysiological Repetition Effects in Persons with Mild Cognitive Impairment depend upon Working Memory Demand.

PubMed

Broster, Lucas S; Jenkins, Shonna L; Holmes, Sarah D; Edwards, Matthew G; Jicha, Gregory A; Jiang, Yang

2018-05-07

Forms of implicit memory, including repetition effects, are preserved relative to explicit memory in clinical Alzheimer's disease. Consequently, cognitive interventions for persons with Alzheimer's disease have been developed that leverage this fact. However, despite the clinical robustness of behavioral repetition effects, altered neural mechanisms of repetition effects are studied as biomarkers of both clinical Alzheimer's disease and pre-morbid Alzheimer's changes in the brain. We hypothesized that the clinical preservation of behavioral repetition effects results in part from concurrent operation of discrete memory systems. We developed two experiments that included probes of emotional repetition effects differing in that one included an embedded working memory task. We found that neural repetition effects manifested in patients with amnestic mild cognitive impairment, the earliest form of clinical Alzheimer's disease, during emotional working memory tasks, but they did not manifest during the task that lacked the embedded working memory manipulation. Specifically, the working memory task evoked neural repetition effects in the P600 time-window, but the same neural mechanism was only minimally implicated in the task without a working memory component. We also found that group differences in behavioral repetition effects were smaller in the experiment with a working memory task. We suggest that cross-domain cognitive challenge can expose "defunct" neural capabilities of individuals with amnestic mild cognitive impairment. Copyright © 2018. Published by Elsevier Ltd.

Decision making in asthma exacerbation: a clinical judgement analysis

PubMed Central

Jenkins, John; Shields, Mike; Patterson, Chris; Kee, Frank

2007-01-01

Background Clinical decisions which impact directly on patient safety and quality of care are made during acute asthma attacks by individual doctors based on their knowledge and experience. Decisions include administration of systemic corticosteroids (CS) and oral antibiotics, and admission to hospital. Clinical judgement analysis provides a methodology for comparing decisions between practitioners with different training and experience, and improving decision making. Methods Stepwise linear regression was used to select clinical cues based on visual analogue scale assessments of the propensity of 62 clinicians to prescribe a short course of oral CS (decision 1), a course of antibiotics (decision 2), and/or admit to hospital (decision 3) for 60 “paper” patients. Results When compared by specialty, paediatricians' models for decision 1 were more likely to include level of alertness as a cue (54% vs 16%); for decision 2 they were more likely to include presence of crepitations (49% vs 16%) and less likely to include inhaled CS (8% vs 40%), respiratory rate (0% vs 24%) and air entry (70% vs 100%). When compared to other grades, the models derived for decision 3 by consultants/general practitioners were more likely to include wheeze severity as a cue (39% vs 6%). Conclusions Clinicians differed in their use of individual cues and the number included in their models. Patient safety and quality of care will benefit from clarification of decision‐making strategies as general learning points during medical training, in the development of guidelines and care pathways, and by clinicians developing self‐awareness of their own preferences. PMID:17428817

Diverse Applications of Nanomedicine

PubMed Central

2017-01-01

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic. PMID:28290206

Health Sciences Librarians and Education: Clinical Librarianship, Consortia, Extraterrestial Telemedicine

ERIC Educational Resources Information Center

Cummings, Polly; And Others

1978-01-01

Three speeches presented by a panel of health science librarians discuss: (1) clinical medical librarianship, with a definition and descriptions of programs in several medical school libraries; (2) consortia, including a definition and reasons for their development; and (3) use of telecommunications for sharing medical information. (MBR)

Preparing Current and Future Practitioners to Integrate Research in Real Practice Settings

ERIC Educational Resources Information Center

Thyer, Bruce A.

2015-01-01

Past efforts aimed at promoting a better integration between research and practice are reviewed. These include the empirical clinical practice movement (ECP), originating within social work; the empirically supported treatment (EST) initiative of clinical psychology; and the evidence-based practice (EBP) model developed within medicine. The…

Symptomatic Acute Toxoplasmosis in Returning Travelers

PubMed Central

Henao-Martínez, Andrés F; Franco-Paredes, Carlos; Palestine, Alan G; Montoya, Jose G

2018-01-01

Abstract We report a family who acquired acute toxoplasmosis after a trip to Central America. One member developed severe clinical manifestations including bilateral chorioretinitis, hepatitis, and myocarditis requiring therapy. Symptomatic acute toxoplasmosis is unusual and possesses a diagnostic challenge. We discuss the clinical and epidemiological implications, laboratory diagnosis, and treatment plan. PMID:29644250

Anatomy Education in Namibia: Balancing Facility Design and Curriculum Development

ERIC Educational Resources Information Center

Wessels, Quenton; Vorster, Willie; Jacobson, Christian

2012-01-01

The anatomy curriculum at Namibia's first, and currently only, medical school is clinically oriented, outcome-based, and includes all of the components of modern anatomical sciences i.e., histology, embryology, neuroanatomy, gross, and clinical anatomy. The design of the facilities and the equipment incorporated into these facilities were directed…

Conducting clinical post-conference in clinical teaching: a qualitative study.

PubMed

Hsu, Li-Ling

2007-08-01

The aim of this study was to explore nurse educators' perceptions regarding clinical postconferences. Additional aims included the exploration of interaction characteristics between students and faculty in clinical postconferences. Nursing students are challenged to think and learn in ways that will prepare them for practice in a complex health care environment. Clinical postconferences give students the opportunity to share knowledge gained through transformative learning and provide a forum for discussion and critical thinking. Faculty members must guide students as the latter participate in discussions, develop problem-solving skills and express feedings and attitudes in clinical conferences. The study used qualitative research methods, including participant observation and an open-ended questionnaire. Participant observers watched interaction activities between teachers and students in clinical postconferences. A total of 20 clinical postconferences, two conferences per teacher, were observed. The Non-Numerical Unstructured Data Indexing Searching and Theory-building qualitative software program was used in data analysis. Research findings indicated that, of the six taxonomy questions, lower-level questions (knowledge and comprehensive questions) were mostly asked by faculty members' postclinical conferences. The most frequently used guideline was task orientation, which is related to practice goals and was found in discussions of assignments, reading reports, discussions of clinical experiences, role plays, psychomotor skill practice, quizzes and student evaluations. It is an essential responsibility of nurse educators to employ postconferences to assist students in applying their knowledge in practical situations, in developing professional values and in enhancing their problem solving abilities.

School-based clinics: their role in helping students meet the 1990 objectives.

PubMed

Dryfoos, J G; Klerman, L V

1988-01-01

Service statistics and observations from site visits across the country indicate that school-based clinics (SBCs) may be having an impact on several of the problems targeted in the 1990 health objectives, including unplanned pregnancy and substance abuse. At least 120 junior and senior high schools in 61 communities are currently operating or developing clinics. Growth is attributed to increasing concern about high-risk youth, especially among educators in their roles of "surrogate parents"; to disillusion with categorical interventions and a movement toward more comprehensive services; and to student, parent, school, and community approval of the new programs. This article describes the comprehensive school-based clinic model, including its history, organizational strategies, school/community partnerships, and services.

Theoretical and clinical perspectives of client stalking behavior.

PubMed

Laskowski, Cheryl

2003-11-01

This article applies theoretical perspectives of client stalking behavior to vignettes of clinical nurse specialists (CNSs) who have experienced stalking incidents. A description of stalking behavior, estimations of the frequency of stalking behavior, characteristics of stalkers, and the impact of stalking on victims are addressed. Health care professionals, including CNSs, may inadvertently become victims of stalking behavior. Firm and clear boundary setting is important in all CNS-client relationships. CNSs who believe that they are becoming the objects of attention for particular individuals are advised to convey a clear message that they have no interest in the development of such a relationship. In this article CNS responses to actual client stalking behavior, including confrontation by the CNS, police involvement, restraining orders, and use of the CNS's attorney, are explored. The use of clinical consultation and the need for agencies to develop safety plans for all employees are also addressed.

Immunomodulatory effect of morphine: therapeutic implications.

PubMed

Dinda, Amit; Gitman, Michael; Singhal, Pravin C

2005-07-01

The immunosuppressive as well as modulatory effects of morphine have been known in clinical medicine for > 100 years. Recent developments in molecular immunology, including experiments in mu (mu) opioid receptor knockout mice has led to a better understanding of central and peripheral mechanisms involved in this process. Though there is a large volume of literature documenting adverse effects of immunosupression following the use of morphine, several reports confirm its potential usefulness as an immunomodulator. In vitro and in vivo animal experiments have demonstrated wide-spectrum effects of morphine, including anti-inflammatory, antifibrotic, antitumour, cardioprotective and renoprotective. Immunomodulation is an important field in modern medicine with rapid advancement in recent years. Though a final statement regarding the clinical relevance of morphine-induced immunomodulation cannot be made at this juncture, nevertheless, it is worthwhile to review current developments. It may encourage further clinical studies to elucidate the influence of morphine treatment on immune regulation in different specialties of medicine.

Multimodal evaluation and management of children with concussion: using our heads and available evidence.

PubMed

Gioia, Gerard A

2015-01-01

Significant attention has been focused on concussions in children, but a dearth of research evidence exists supporting clinical evaluation and management. The primary objective of this review paper is to describe a multimodal, developmentally adapted, standardized concussion assessment and active rehabilitation approach for children as young as 5 years old. This study reviews the CDC-funded research programme, including the development of tools for post-concussion symptom assessment involving the child and parent, measurement of specific neurocognitive functions and assessment of dynamic cognitive exertional effects. A clinical approach to active, individualized, moderated concussion rehabilitation management is presented, including a 10-step guide to symptom management, with a specific focus on the school challenges faced by the recovering student. To better inform concussion practice across the developmental age spectrum, a significant need exists for further research evidence to refine clinical assessment methods and develop effective treatment approaches.

Multimodal Evaluation and Management of Children with Concussion: Using our heads and available evidence

PubMed Central

Gioia, Gerard A.

2015-01-01

Significant attention has been focused on concussions in children but a dearth of research evidence exists supporting clinical evaluation and management. The primary objective of this review paper is to describe a multimodal, developmentally adapted, standardized concussion assessment and active rehabilitation approach for children as young as age five. We review our CDC-funded research program including the development of tools for post-concussion symptom assessment involving the child and parent, measurement of specific neurocognitive functions, and assessment of dynamic cognitive exertional effects. A clinical approach to active, individualized, moderated concussion rehabilitation management is presented, including a ten step guide to symptom management, with a specific focus on the school challenges faced by the recovering student. To better inform concussion practice across the developmental age spectrum, a significant need exists for further research evidence to refine our clinical assessment methods and develop effective treatment approaches. PMID:25356518

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

PubMed Central

Gwinn, Katrina; David, Karen K; Swanson-Fischer, Christine; Albin, Roger; Hillaire-Clarke, Coryse St; Sieber, Beth-Anne; Lungu, Codrin; Bowman, F DuBois; Alcalay, Roy N; Babcock, Debra; Dawson, Ted M; Dewey, Richard B; Foroud, Tatiana; German, Dwight; Huang, Xuemei; Petyuk, Vlad; Potashkin, Judith A; Saunders-Pullman, Rachel; Sutherland, Margaret; Walt, David R; West, Andrew B; Zhang, Jing; Chen-Plotkin, Alice; Scherzer, Clemens R; Vaillancourt, David E; Rosenthal, Liana S

2017-01-01

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset. PMID:28644039

Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

PubMed Central

Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

2016-01-01

Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

Use of atypical antipsychotics for treatment-resistant major depressive disorder.

PubMed

Papakostas, George I; Shelton, Richard C

2008-12-01

Despite the progressive increase in the number of pharmacologic agents with potential antidepressant activity, many patients suffering from major depressive disorder (MDD) continue to be symptomatic. Clearly, an urgent need exists to develop safer, better tolerated, and more effective treatments for MDD. Use of atypical antipsychotic agents as adjunctive treatment for treatment-resistant MDD (TRD) represents one such effort toward novel pharmacotherapy development. Atypical antipsychotic agents have been hypothesized to be beneficial in treating mood disorders, including TRD, as a result of their complex mechanisms of action. After an initial series of positive case reports, series, and small clinical trials, subsequent larger-scale projects have yielded conflicting results. However, more recently, larger-scale clinical trials have supported the effectiveness of at least some of these medications. This review summarizes the existing data regarding the effectiveness of these medications in treating TRD, including biochemical rationale and clinical data.

Biomarkers as drug development tools: discovery, validation, qualification and use.

PubMed

Kraus, Virginia B

2018-06-01

The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

A method for developing outcome measures in the clinical laboratory.

PubMed

Jones, J

1996-01-01

Measuring and reporting outcomes in health care is becoming more important for quality assessment, utilization assessment, accreditation standards, and negotiating contracts in managed care. How does one develop an outcome measure for the laboratory to assess the value of the services? A method is described which outlines seven steps in developing outcome measures for a laboratory service or process. These steps include the following: 1. Identify the process or service to be monitored for performance and outcome assessment. 2. If necessary, form an multidisciplinary team of laboratory staff, other department staff, physicians, and pathologists. 3. State the purpose of the test or service including a review of published data for the clinical pathological correlation. 4. Prepare a process cause and effect diagram including steps critical to the outcome. 5. Identify key process variables that contribute to positive or negative outcomes. 6. Identify outcome measures that are not process measures. 7. Develop an operational definition, identify data sources, and collect data. Examples, including a process cause and effect diagram, process variables, and outcome measures, are given using the Therapeutic Drug Monitoring service (TDM). A summary of conclusions and precautions for outcome measurement is then provided.

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

PubMed Central

Bianco, Antonio C.; Bauer, Andrew J.; Burman, Kenneth D.; Cappola, Anne R.; Celi, Francesco S.; Cooper, David S.; Kim, Brian W.; Peeters, Robin P.; Rosenthal, M. Sara; Sawka, Anna M.

2014-01-01

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. Results: We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non–levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. Conclusions: We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine–liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile. PMID:25266247

Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.

PubMed

Jonklaas, Jacqueline; Bianco, Antonio C; Bauer, Andrew J; Burman, Kenneth D; Cappola, Anne R; Celi, Francesco S; Cooper, David S; Kim, Brian W; Peeters, Robin P; Rosenthal, M Sara; Sawka, Anna M

2014-12-01

A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non-levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine-liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.

Methodology for the systematic reviews on an adjacent segment pathology.

PubMed

Norvell, Daniel C; Dettori, Joseph R; Skelly, Andrea C; Riew, K Daniel; Chapman, Jens R; Anderson, Paul A

2012-10-15

A systematic review. To provide a detailed description of the methods undertaken in the systematic search and analytical summary of adjacent segment pathology (ASP) issues and to describe the process used to develop consensus statements and clinical recommendations regarding factors associated with the prevention and treatment of ASP. We present methods used in conducting the systematic, evidence-based reviews and development of expert panel consensus statements and clinical recommendations on the classification, natural history, risk factors, and treatment of radiographical and clinical ASP. Our intent is that clinicians will combine the information from these reviews with an understanding of their own capacities and experience to better manage patients at risk of ASP and consider future research for the prevention and treatment of ASP. A systematic search and critical review of the English-language literature was undertaken for articles published on the classification, risk, risk factors, and treatment of radiographical and clinical ASP. Articles were screened for relevance using a priori criteria, and relevant articles were critically reviewed. Whether an article was included for review depended on whether the study question was descriptive, one of therapy, or one of prognosis. The strength of evidence for the overall body of literature in each topic area was determined by 2 independent reviewers considering risk of bias, consistency, directness, and precision of results using a modification of the Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria. Disagreements were resolved by consensus. Findings from articles meeting inclusion criteria were summarized. From these summaries, consensus statements or clinical recommendations were formulated among subject experts through a modified Delphi process using the GRADE approach. A total of 3382 articles were identified and screened on 14 topics relating to the classification, risks, risk factors, and treatment of radiographical and clinical ASP. Of these, 127 met our predetermined inclusion criteria and were used to answer specific clinical questions within each topic. Lack of precision in the terminology related to adjacent segment disease and critical evaluation of definitions used across included articles led to a consensus to use ASP and suggest it as a standard. No validated comprehensive classification system for ASP currently exists. The expert panel developed a consensus definition of radiographical and clinical ASP (RASP and CASP). Some of the highlights from the analyses included the annual, 5- and 10-year risks of developing cervical and lumbar ASP after surgery, several important risk factors associated with the development of cervical and lumbar ASP, and the possibility that some motion sparing procedures may be associated with a lower risk of ASP compared with fusion despite kinematic studies demonstrating similar adjacent segment mobility following these procedures. Other highlights included a high risk of proximal junctional kyphosis (PJK) following long fusions for deformity correction, postsurgical malalignment as a potential risk factor for RASP and the paucity of studies on treatment of cervical and lumbar ASP. Systematic reviews were undertaken to understand the classification, risks, risk factors, and treatment of RASP and CASP and to provide consensus statements and clinical recommendations. This article reports the methods used in the reviews.

Development of a hospital-based patient-reported outcome framework for lung cancer patients: a study protocol.

PubMed

Moloczij, Natasha; Gough, Karla; Solomon, Benjamin; Ball, David; Mileshkin, Linda; Duffy, Mary; Krishnasamy, Mei

2018-01-11

Patient-reported outcome (PRO) data is central to the delivery of quality health care. Establishing sustainable, reliable and cost-efficient methods for routine collection and integration of PRO data into health information systems is challenging. This protocol paper describes the design and structure of a study to develop and pilot test a PRO framework to systematically and longitudinally collect PRO data from a cohort of lung cancer patients at a comprehensive cancer centre in Australia. Best-practice guidelines for developing registries aimed at collecting PROs informed the development of this PRO framework. Framework components included: achieving consensus on determining the purpose of the framework, the PRO measures to be included, the data collection time points and collection methods (electronic and paper), establishing processes to safeguard the quality of the data collected and to link the PRO framework to an existing hospital-based lung cancer clinical registry. Lung cancer patients will be invited to give feedback on the PRO measures (PROMs) chosen and the data collection time points and methods. Implementation of the framework will be piloted for 12 months. Then a mixed-methods approach used to explore patient and multidisciplinary perspectives on the feasibility of implementing the framework and linking it to the lung cancer clinical registry, its clinical utility, perceptions of data collection burden, and preliminary assessment of resource costs to integrate, implement and sustain the PRO framework. The PRO data set will include: a quality of life questionnaire (EORTC-QLQ-C30) and the EORTC lung cancer specific module (QLQC-LC-13). These will be collected pre-treatment (baseline), 2, 6 and 12 months post-baseline. Also, four social isolation questions (PROMIS) will be collected at baseline. Identifying and deciding on the overall purpose, clinical utility of data and which PROs to collect from patients requires careful consideration. Our study will explore how PRO data collection processes that link to a clinical data set can be developed and integrated; how PRO systems that are easy for patients to complete and professionals to use in practice can be achieved, and will provide indicative costs of developing and integrating a longitudinal PRO framework into routine hospital data collection systems. This study is not a clinical trial and is therefore not registered in any trial registry. However, it has received human research ethics approval (LNR/16/PMCC/45).

Clinical predictors of vestibulo-ocular dysfunction in pediatric sports-related concussion.

PubMed

Ellis, Michael J; Cordingley, Dean M; Vis, Sara; Reimer, Karen M; Leiter, Jeff; Russell, Kelly

2017-01-01

OBJECTIVE There were 2 objectives of this study. The first objective was to identify clinical variables associated with vestibulo-ocular dysfunction (VOD) detected at initial consultation among pediatric patients with acute sports-related concussion (SRC) and postconcussion syndrome (PCS). The second objective was to reexamine the prevalence of VOD in this clinical cohort and evaluate the effect of VOD on length of recovery and the development of PCS. METHODS A retrospective review was conducted for all patients with acute SRC and PCS who were evaluated at a pediatric multidisciplinary concussion program from September 2013 to May 2015. Acute SRS was defined as presenting < 30 days postinjury, and PCS was defined according to the International Classification of Diseases, 10th Revision criteria and included being symptomatic 30 days or longer postinjury. The initial assessment included clinical history and physical examination performed by 1 neurosurgeon. Patients were assessed for VOD, defined as the presence of more than 1 subjective vestibular and oculomotor complaint (dizziness, diplopia, blurred vision, etc.) and more than 1 objective physical examination finding (abnormal near point of convergence, smooth pursuits, saccades, or vestibulo-ocular reflex testing). Poisson regression analysis was used to identify factors that increased the risk of VOD at initial presentation and the development of PCS. RESULTS Three hundred ninety-nine children, including 306 patients with acute SRC and 93 with PCS, were included. Of these patients, 30.1% of those with acute SRC (65.0% male, mean age 13.9 years) and 43.0% of those with PCS (41.9% male, mean age 15.4 years) met the criteria for VOD at initial consultation. Independent predictors of VOD at initial consultation included female sex, preinjury history of depression, posttraumatic amnesia, and presence of dizziness, blurred vision, or difficulty focusing at the time of injury. Independent predictors of PCS among patients with acute SRC included the presence of VOD at initial consultation, preinjury history of depression, and posttraumatic amnesia at the time of injury. CONCLUSIONS This study identified important potential risk factors for the development of VOD following pediatric SRC. These results provide confirmatory evidence that VOD at initial consultation is associated with prolonged recovery and is an independent predictor for the development of PCS. Future studies examining clinical prediction rules in pediatric concussion should include VOD. Additional research is needed to elucidate the natural history of VOD following SRC and establish evidence-based indications for targeted vestibular rehabilitation.

Development of a Learning-Oriented Computer Assisted Instruction Designed to Improve Skills in the Clinical Assessment of the Nutritional Status: A Pilot Evaluation

PubMed Central

García de Diego, Laura; Cuervo, Marta; Martínez, J. Alfredo

2015-01-01

Computer assisted instruction (CAI) is an effective tool for evaluating and training students and professionals. In this article we will present a learning-oriented CAI, which has been developed for students and health professionals to acquire and retain new knowledge through the practice. A two-phase pilot evaluation was conducted, involving 8 nutrition experts and 30 postgraduate students, respectively. In each training session, the software developed guides users in the integral evaluation of a patient’s nutritional status and helps them to implement actions. The program includes into the format clinical tools, which can be used to recognize possible patient’s needs, to improve the clinical reasoning and to develop professional skills. Among them are assessment questionnaires and evaluation criteria, cardiovascular risk charts, clinical guidelines and photographs of various diseases. This CAI is a complete software package easy to use and versatile, aimed at clinical specialists, medical staff, scientists, educators and clinical students, which can be used as a learning tool. This application constitutes an advanced method for students and health professionals to accomplish nutritional assessments combining theoretical and empirical issues, which can be implemented in their academic curriculum. PMID:25978456

Development of a learning-oriented computer assisted instruction designed to improve skills in the clinical assessment of the nutritional status: a pilot evaluation.

PubMed

García de Diego, Laura; Cuervo, Marta; Martínez, J Alfredo

2015-01-01

Computer assisted instruction (CAI) is an effective tool for evaluating and training students and professionals. In this article we will present a learning-oriented CAI, which has been developed for students and health professionals to acquire and retain new knowledge through the practice. A two-phase pilot evaluation was conducted, involving 8 nutrition experts and 30 postgraduate students, respectively. In each training session, the software developed guides users in the integral evaluation of a patient's nutritional status and helps them to implement actions. The program includes into the format clinical tools, which can be used to recognize possible patient's needs, to improve the clinical reasoning and to develop professional skills. Among them are assessment questionnaires and evaluation criteria, cardiovascular risk charts, clinical guidelines and photographs of various diseases. This CAI is a complete software package easy to use and versatile, aimed at clinical specialists, medical staff, scientists, educators and clinical students, which can be used as a learning tool. This application constitutes an advanced method for students and health professionals to accomplish nutritional assessments combining theoretical and empirical issues, which can be implemented in their academic curriculum.

The role of the clinical nurse specialist/neonatal nurse practitioner in a breastfeeding clinic: a model of advanced practice.

PubMed

Gibbins, S A; Green, P E; Scott, P A; MacDonell, J W

2000-03-01

A commitment to quality health care requires the development of innovative models of care. An example of such a model is the Clinical Nurse Specialist/Neonatal Nurse Practitioner in the role as consultant to Lactation Consultants in a large breastfeeding clinic. The role of the Clinical Nurse Specialist/Neonatal Nurse Practitioner in this ambulatory setting encompasses all the dimensions of the advanced practice model including research, leadership, education, and clinical practice. The evolution of this model of care is described. A conceptual framework of this advanced practice model is presented, supported by examples of the role in the clinic.

Asking good clinical research questions and choosing the right study design.

PubMed

Bragge, P

2010-07-01

Clinicians and researchers seek answers to clinical research questions, primarily by accessing the results of clinical research studies. This paper moves the focus of research enquiry from getting answers to developing good clinical research questions. Using worked examples, the steps involved in refining questions drawn from various sources to create 'answerable' clinical research questions using the 'PICO' principle are described. Issues to consider in prioritising clinical research questions are also identified. Theoretical and practical considerations involved in choosing the right study design for a clinical research question are then discussed using the worked examples. These include: Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Development of the Canadian Physiotherapy Assessment of Clinical Performance: A New Tool to Assess Physiotherapy Students' Performance in Clinical Education.

PubMed

Mori, Brenda; Brooks, Dina; Norman, Kathleen E; Herold, Jodi; Beaton, Dorcas E

2015-08-01

To develop the first draft of a Canadian tool to assess physiotherapy (PT) students' performance in clinical education (CE). Phase 1: to gain consensus on the items within the new tool, the number and placement of the comment boxes, and the rating scale; Phase 2: to explore the face and content validity of the draft tool. Phase 1 used the Delphi method; Phase 2 used cognitive interviewing methods with recent graduates and clinical instructors (CIs) and detailed interviews with clinical education and measurement experts. Consensus was reached on the first draft of the new tool by round 3 of the Delphi process, which was completed by 21 participants. Interviews were completed with 13 CIs, 6 recent graduates, and 7 experts. Recent graduates and CIs were able to interpret the tool accurately, felt they could apply it to a recent CE experience, and provided suggestions to improve the draft. Experts provided salient advice. The first draft of a new tool to assess PT students in CE, the Canadian Physiotherapy Assessment of Clinical Performance (ACP), was developed and will undergo further development and testing, including national consultation with stakeholders. Data from Phase 2 will contribute to developing an online education module for CIs and students.

Medications Development for the Treatment of Alcohol Use Disorder: Insights into the Predictive Value of Animal and Human Laboratory Models

PubMed Central

Yardley, Megan M.; Ray, Lara A.

2016-01-01

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research. PMID:26833803

Introduction to a Special Issue of the Journal of Immunological Methods: Building global resource programs to support HIV/AIDS clinical trial studies.

PubMed

Sanchez, Ana M; Denny, Thomas N; O'Gorman, Maurice

2014-07-01

This Special Issue of the Journal of Immunological Methods includes 16 manuscripts describing quality assurance activities related to virologic and immunologic monitoring of six global laboratory resource programs that support international HIV/AIDS clinical trial studies: Collaboration for AIDS Vaccine Discovery (CAVD); Center for HIV/AIDS Vaccine Immunology (CHAVI); External Quality Assurance Program Oversight Laboratory (EQAPOL); HIV Vaccine Trial Network (HVTN); International AIDS Vaccine Initiative (IAVI); and Immunology Quality Assessment (IQA). The reports from these programs address the many components required to develop comprehensive quality control activities and subsequent quality assurance programs for immune monitoring in global clinical trials including: all aspects of processing, storing, and quality assessment of PBMC preparations used ubiquitously in HIV clinical trials, the development and optimization of assays for CD8 HIV responses and HIV neutralization, a comprehensive global HIV virus repository, and reports on the development and execution of novel external proficiency testing programs for immunophenotyping, intracellular cytokine staining, ELISPOT and luminex based cytokine measurements. In addition, there are articles describing the implementation of Good Clinical Laboratory Practices (GCLP) in a large quality assurance laboratory, the development of statistical methods specific for external proficiency testing assessment, a discussion on the ability to set objective thresholds for measuring rare events by flow cytometry, and finally, a manuscript which addresses a framework for the structured reporting of T cell immune function based assays. It is anticipated that this series of manuscripts covering a wide range of quality assurance activities associated with the conduct of global clinical trials will provide a resource for individuals and programs involved in improving the harmonization, standardization, accuracy, and sensitivity of virologic and immunologic testing. Copyright © 2014 Elsevier B.V. All rights reserved.

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria.

PubMed

Burden-Teh, E; Phillips, R C; Thomas, K S; Ratib, S; Grindlay, D; Murphy, R

2017-11-06

The diagnosis of psoriasis in adults and children is made clinically, for both patient management and the selection of participants in research. Diagnostic criteria provide a structure for clinical assessment, which in turn helps standardize patient recruitment into clinical trials and case definitions in observational studies. The aim of this systematic review was to identify and critically appraise the published studies to date that had a primary research aim to develop or validate diagnostic criteria for psoriasis. A search of Ovid MEDLINE and Ovid Embase was conducted in October 2016. The primary objective was to record the sensitivity and specificity of diagnostic criteria for psoriasis. Secondary objectives included diagnostic recommendations, applicability to children and study characteristics. Diagnostic accuracy studies were critically appraised for risk of bias using the QUADAS-2 tool. Twenty-three studies met the inclusion criteria. None detailed clinical examination-based diagnostic criteria. The included criteria varied from genetic and molecular diagnostic models to skin imaging, histopathology, and questionnaire-based, computer-aided and traditional Chinese medicine criteria. High sensitivity and specificity (> 90%) were reported in many studies. However, the study authors often did not specify how the criteria would be used clinically or in research. This review identified studies with varying risk of bias, and due to each study developing separate criteria meta-analysis was not possible. Clinical examination-based diagnostic criteria are currently lacking for psoriasis. Future research could follow an international collaborative approach and employ study designs allowing high-quality diagnostic accuracy testing. Existing and newly developed criteria require validation. © 2017 British Association of Dermatologists.

Developing a science of clinical utility in diagnostic classification systems field study strategies for ICD-11 mental and behavioral disorders.

PubMed

Keeley, Jared W; Reed, Geoffrey M; Roberts, Michael C; Evans, Spencer C; Medina-Mora, María Elena; Robles, Rebeca; Rebello, Tahilia; Sharan, Pratap; Gureje, Oye; First, Michael B; Andrews, Howard F; Ayuso-Mateos, José Luís; Gaebel, Wolfgang; Zielasek, Juergen; Saxena, Shekhar

2016-01-01

The World Health Organization (WHO) Department of Mental Health and Substance Abuse has developed a systematic program of field studies to evaluate and improve the clinical utility of the proposed diagnostic guidelines for mental and behavioral disorders in the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11). The clinical utility of a diagnostic classification is critical to its function as the interface between health encounters and health information, and to making the ICD-11 be a more effective tool for helping the WHO's 194 member countries, including the United States, reduce the global disease burden of mental disorders. This article describes the WHO's efforts to develop a science of clinical utility in regard to one of the two major classification systems for mental disorders. We present the rationale and methodologies for an integrated and complementary set of field study strategies, including large international surveys, formative field studies of the structure of clinicians' conceptualization of mental disorders, case-controlled field studies using experimental methodologies to evaluate the impact of proposed changes to the diagnostic guidelines on clinicians' diagnostic decision making, and ecological implementation field studies of clinical utility in the global settings in which the guidelines will ultimately be implemented. The results of these studies have already been used in making decisions about the structure and content of ICD-11. If clinical utility is indeed among the highest aims of diagnostic systems for mental disorders, as their developers routinely claim, future revision efforts should continue to build on these efforts. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Quality information for quality use of medicines; 2nd International Conference, Kazan, 15-16 October 2010.

PubMed

Ziganshina, Lilia E; Menkes, David B; Herxheimer, Andrew

2011-01-01

Kazan hosted Russia's first international conference on medicines that was entirely independent of the pharmaceutical industry, attracting 414 participants from 9 countries and 20 regions of the Russian Federation. The meeting was greeted and endorsed by world leaders in pharmaceutical information, policy and regulation. Delegates discussed the professional and social problems arising from unethical drug promotion, including compromised evidence from clinical trials and consequent impairments in health service delivery. The Conference adopted a resolution prioritizing policy development and health system needs, notably including the development of clinical pharmacology. A website documents conference materials and provides an interface for future collaboration: http://evidenceupdate-tatarstan.ru/confer.

Improving the quality of care for women with cardiovascular disease: report of a DCRI Think Tank, March 8 to 9, 2007.

PubMed

Berger, Jeffrey S; Bairey-Merz, C Noel; Redberg, Rita F; Douglas, Pamela S

2008-11-01

Differences in pathophysiology, diagnosis, and treatment of women with cardiovascular disease compared with men has become a major focus during the past decade. Nevertheless, little attention has focused on improving the quality of healthcare in women compared with other areas of cardiovascular medicine. To address this deficit, Duke University Medical Center convened a national Duke Clinical Research Institute (DCRI) Think Tank meeting, including basic science and clinical researchers, payers, legislators, clinical experts, government regulators, and members of the pharmaceutical and device industries. This report provides an overview of the discussions and proposed solutions. Discussion concentrated on the development of strategies to improve the quality of health care for women with heart disease. Key components to improve quality care include: (1) enhance the quantity and quality of evidence-based medicine to guide care in women through improvements in trial design, enrollment and retention of women subjects, results analysis and reporting, and better incentives to perform research in women; (2) provide incentives to develop better data in women through mandating changes in the drug and device development and approval processes; (3) incorporate specific recommendations for women into guidelines when data are sufficient; and (4) apply proven sex-based differences in risk stratification, diagnostic testing, and drug usage and dosing in clinical care. Examples of possible strategies are included. The above approach represents a necessary, but not sufficient, platform to improve the overall quality of healthcare in women with cardiovascular disease.

The Southeast Asian Influenza Clinical Research Network: development and challenges for a new multilateral research endeavor.

PubMed

Higgs, Elizabeth S; Hayden, Frederick G; Chotpitayasunondh, Tawee; Whitworth, Jimmy; Farrar, Jeremy

2008-04-01

The Southeast Asia Influenza Clinical Research Network (SEA ICRN) (www.seaclinicalresearch.org) is a recently developed multilateral, collaborative partnership that aims to advance scientific knowledge and management of human influenza through integrated clinical investigation. The partnership of hospitals and institutions in Indonesia, Thailand, United Kingdom, United States, and Viet Nam was established in late 2005 after agreement on the general principles and mission of the initiative and after securing initial financial support. The establishment of the SEA ICRN was both a response to the re-emergence of the highly pathogenic avian influenza A(H5N1) virus in Southeast Asia in late 2003 and an acknowledgment that clinical trials on emerging infectious diseases require prepared and coordinated research capacity. The objectives of the Network also include building sustainable research capacity in the region, compliance with international standards, and prompt dissemination of information and sharing of samples. The scope of research includes diagnosis, pathogenesis, treatment and prevention of human influenza due to seasonal or novel viruses. The Network has overcome numerous logistical and scientific challenges but has now successfully initiated several clinical trials. The establishment of a clinical research network is a vital part of preparedness and an important element during an initial response phase to a pandemic.

A historical overview of magnetic resonance imaging, focusing on technological innovations.

PubMed

Ai, Tao; Morelli, John N; Hu, Xuemei; Hao, Dapeng; Goerner, Frank L; Ager, Bryan; Runge, Val M

2012-12-01

Magnetic resonance imaging (MRI) has now been used clinically for more than 30 years. Today, MRI serves as the primary diagnostic modality for many clinical problems. In this article, historical developments in the field of MRI will be discussed with a focus on technological innovations. Topics include the initial discoveries in nuclear magnetic resonance that allowed for the advent of MRI as well as the development of whole-body, high field strength, and open MRI systems. Dedicated imaging coils, basic pulse sequences, contrast-enhanced, and functional imaging techniques will also be discussed in a historical context. This article describes important technological innovations in the field of MRI, together with their clinical applicability today, providing critical insights into future developments.

PDT in clinics: indications, results, and markets.

PubMed

Patrice, Thierry; Olivier, David; Bourre, Ludovic

2006-01-01

Photodynamic therapy (PDT) is based on the selective light activation of an exogenously given drug to patients. PDT acts mainly on cell membranes either of neovascular endothelial cells or of cancer cells leading to cancer cell death. Six drugs are now marketed based on clinical assays in various indications, which showed a clear cost efficiency as compared to other classical procedures. PDT is easy to handle and can be performed in medical installations fitting the conditions of health care in developing countries. Its cost effectiveness could represent an appropriate solution to the increasing number of cancers of various origin. However despite all the clinical results now available, PDT development remains slow. The reasons for this situation include cost of development, intellectual property, and competition between pharmaceutical companies.

[Development and application of emergency medical information management system].

PubMed

Wang, Fang; Zhu, Baofeng; Chen, Jianrong; Wang, Jian; Gu, Chaoli; Liu, Buyun

2011-03-01

To meet the needs of clinical practice of rescuing critical illness and develop the information management system of the emergency medicine. Microsoft Visual FoxPro, which is one of Microsoft's visual programming tool, is used to develop computer-aided system included the information management system of the emergency medicine. The system mainly consists of the module of statistic analysis, the module of quality control of emergency rescue, the module of flow path of emergency rescue, the module of nursing care in emergency rescue, and the module of rescue training. It can realize the system management of emergency medicine and,process and analyze the emergency statistical data. This system is practical. It can optimize emergency clinical pathway, and meet the needs of clinical rescue.

Post-procedural Care in Interventional Radiology: What Every Interventional Radiologist Should Know—Part I: Standard Post-procedural Instructions and Follow-Up Care

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taslakian, Bedros, E-mail: Bedros.Taslakian@nyumc.org; Sridhar, Divya

Interventional radiology (IR) has evolved into a full-fledged clinical specialty with attendant patient care responsibilities. Success in IR now requires development of a full clinical practice, including consultations, inpatient admitting privileges, and an outpatient clinic. In addition to technical excellence and innovation, maintaining a comprehensive practice is imperative for interventional radiologists to compete successfully for patients and referral bases. A structured approach to periprocedural care, including routine follow-up and early identification and management of complications, facilitates efficient and thorough management with an emphasis on quality and patient safety.

Translational bioinformatics: linking the molecular world to the clinical world.

PubMed

Altman, R B

2012-06-01

Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.

Post-procedural Care in Interventional Radiology: What Every Interventional Radiologist Should Know-Part I: Standard Post-procedural Instructions and Follow-Up Care.

PubMed

Taslakian, Bedros; Sridhar, Divya

2017-04-01

Interventional radiology (IR) has evolved into a full-fledged clinical specialty with attendant patient care responsibilities. Success in IR now requires development of a full clinical practice, including consultations, inpatient admitting privileges, and an outpatient clinic. In addition to technical excellence and innovation, maintaining a comprehensive practice is imperative for interventional radiologists to compete successfully for patients and referral bases. A structured approach to periprocedural care, including routine follow-up and early identification and management of complications, facilitates efficient and thorough management with an emphasis on quality and patient safety.

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Fleseriu, Maria; Hashim, Ibrahim A; Karavitaki, Niki; Melmed, Shlomo; Murad, M Hassan; Salvatori, Roberto; Samuels, Mary H

2016-11-01

To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

Clinical audit in the final year of undergraduate medical education: towards better care of future generations.

PubMed

Mak, Donna B; Miflin, Barbara

2012-01-01

In Australia, in an environment undergoing rapidly changing requirements for health services, there is an urgent need for future practitioners to be knowledgeable, skilful and self-motivated in ensuring the quality and safety of their practice. Postgraduate medical education and vocational programs have responded by incorporating training in quality improvement into continuing professional development requirements, but undergraduate medical education has been slower to respond. This article describes the clinical audit programme undertaken by all students in the final year of the medical course at the University of Notre Dame, Fremantle, Australia, and examines the educational worth of this approach. Data were obtained from curricular documents, including the clinical audit handbook, and from evaluation questionnaires administered to students and supervisors. The clinical audit programme is based on sound educational principles, including situated and participatory learning and reflective practice. It has demonstrated multi-dimensional benefits for students in terms of learning the complexities of conducting an effective audit in professional practice, and for health services in terms of facilitating quality improvement. Although this programme was developed in a medical course, the concept is readily transferable to a variety of other health professional curricula in which students undertake clinical placements.

Australasian emergency physicians: a learning and educational needs analysis. Part one: background and methodology. Profile of FACEM.

PubMed

Dent, Andrew W; Asadpour, Ali; Weiland, Tracey J; Paltridge, Debbie

2008-02-01

Fellows of the Australasian College for Emergency Medicine (FACEM) have opportunities to participate in a range of continuing professional development activities. To inform FACEM and assist those involved in planning continuing professional development interventions for FACEM, we undertook a learning needs analysis of emergency physicians. Exploratory study using survey methodology. Following questionnaire development by iterative feedback with emergency physicians and researchers, a mailed survey was distributed to all FACEM. The survey comprised eight items on work and demographic characteristics of FACEM, and 194 items on attitudes to existing learning opportunities, barriers to learning, and perceived learning needs and preferences. Fifty-eight percent (503/854) of all FACEM surveyed responded to the questionnaire, almost half of whom attained their FACEM after year 2000. The sample comprised mostly males (72.8%) with mean age of the sample 41.6 years, similar to ACEM database. Most respondents reported working in ACEM accredited hospitals (89%), major referral hospitals (54%), and practiced on both children and adults (78%). FACEM reported working on average 26.7 clinical hours per week with those at private hospitals working a greater proportion of clinical hours than other hospital types. As the first of six related reports, this paper documents the methodology used, including questionnaire development, and provides the demographics of responding FACEM, including the clinical and non-clinical hours worked and type of hospital of principal employment.

Developmental procedures for the clinical practice guidelines for conscious sedation in dentistry for the Korean Academy of Dental Sciences.

PubMed

An, So-Youn; Seo, Kwang-Suk; Kim, Seungoh; Kim, Jongbin; Lee, Deok-Won; Hwang, Kyung-Gyun; Kim, Hyun Jeong

2016-12-01

Evidence-based clinical practice guidelines (CPGs) are defined as "statements that are scientifically reviewed about evidence and systematically developed to assist in the doctors' and patients' decision making in certain clinical situations." This recommendation aims to promote good clinical practice for the provision of safe and effective practices of conscious sedation in dentistry. The development of this clinical practice guideline was conducted by performing a systematic search of the literature for evidence-based CPGs. Existing guidelines, relevant systematic reviews, policy documents, legislation, or other recommendations were reviewed and appraised. To supplement this information, key questions were formulated by the Guideline Development Group and used as the basis for designing systematic literature search strategies to identify literature that may address these questions. Guideline documents were evaluated through a review of domestic and international databases for the development of a renewing of existing conscious sedation guidelines for dentistry. Clinical practice guidelines were critically appraised for their methodologies using Appraisal of guidelines for research and evaluation (AGREE) II. A total of 12 existing CPGs were included and 13 recommendations were made in a range of general, adult, and pediatric areas. The clinical practice guidelines for conscious sedation will be reviewed in 5 years' time for further updates to reflect significant changes in the field.

Adolescent Brain and Cognitive Developments: Implications for Clinical Assessment in Traumatic Brain Injury

ERIC Educational Resources Information Center

Ciccia, Angela Hein; Meulenbroek, Peter; Turkstra, Lyn S.

2009-01-01

Adolescence is a time of significant physical, social, and emotional developments, accompanied by changes in cognitive and language skills. Underlying these are significant developments in brain structures and functions including changes in cortical and subcortical gray matter and white matter tracts. Among the brain regions that develop during…

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

Video observation in HIT development: lessons learned on benefits and challenges.

PubMed

Høstgaard, Anna Marie; Bertelsen, Pernille

2012-08-22

Experience shows that the precondition for the development of successful health information technologies is a thorough insight into clinical work practice. In contemporary clinical work practice, clinical work and health information technology are integrated, and part of the practice is tacit. When work practice becomes routine, it slips to the background of the conscious awareness and becomes difficult to recognize without the context to support recall. This means that it is difficult to capture with traditional ethnographic research methods or in usability laboratories or clinical set ups. Observation by the use of the video technique within healthcare settings has proven to be capable of providing a thorough insight into the complex clinical work practice and its context - including parts of the tacit practice. The objective of this paper is 1) to argue for the video observation technique to inform and improve health-information-technology development and 2) to share insights and lessons learned on benefits and challenges when using the video observation technique within healthcare settings. A multiple case study including nine case studies conducted by DaCHI researchers 2004-2011 using audio-visual, non-participant video observation for data collection within different healthcare settings. In HIT development, video observation is beneficial for 1) informing and improving system design 2) studying changes in work practice 3) identifying new potentials and 4) documenting current work practices. The video observation technique used within healthcare settings is superior to other ethnographic research methods when it comes to disclosing the complexity in clinical work practice. The insights gained are far more realistic compared to traditional ethnographic studies or usability studies and studies in clinical set ups. Besides, the data generated through video recordings provide a solid basis for dialog between the health care professionals involved. The most important lessons learned are that a well considered methodology and clear formulated objectives are imperative, in order to stay focused during the data rich analysis phase. Additionally, the video observation technique is primarily recommended for studies of specific clinical work practices within delimited clinical settings. Overall, the video observation technique has proven to be capable of improving our understanding of the interwoven relation between clinical work practice and HIT and to inform us about user requirements and needs for HIT, which is a precondition for the development of more successful HIT systems in the future.

Design of Phase I Combination Trials: Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee

PubMed Central

Paller, Channing J.; Bradbury, Penelope A.; Ivy, S. Percy; Seymour, Lesley; LoRusso, Patricia M.; Baker, Laurence; Rubinstein, Larry; Huang, Erich; Collyar, Deborah; Groshen, Susan; Reeves, Steven; Ellis, Lee M.; Sargent, Daniel J.; Rosner, Gary L.; LeBlanc, Michael L.; Ratain, Mark J.

2014-01-01

Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistical and regulatory challenges. The phase 1 trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee developed a set of recommendations for the phase 1 development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biological or pharmacological rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase 1 clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamic (i.e., biomarker). PMID:25125258

The process of developing audiovisual patient information: challenges and opportunities.

PubMed

Hutchison, Catherine; McCreaddie, May

2007-11-01

The aim of this project was to produce audiovisual patient information, which was user friendly and fit for purpose. The purpose of the audiovisual patient information is to inform patients about randomized controlled trials, as a supplement to their trial-specific written information sheet. Audiovisual patient information is known to be an effective way of informing patients about treatment. User involvement is also recognized as being important in the development of service provision. The aim of this paper is (i) to describe and discuss the process of developing the audiovisual patient information and (ii) to highlight the challenges and opportunities, thereby identifying implications for practice. A future study will test the effectiveness of the audiovisual patient information in the cancer clinical trial setting. An advisory group was set up to oversee the project and provide guidance in relation to information content, level and delivery. An expert panel of two patients provided additional guidance and a dedicated operational team dealt with the logistics of the project including: ethics; finance; scriptwriting; filming; editing and intellectual property rights. Challenges included the limitations of filming in a busy clinical environment, restricted technical and financial resources, ethical needs and issues around copyright. There were, however, substantial opportunities that included utilizing creative skills, meaningfully involving patients, teamworking and mutual appreciation of clinical, multidisciplinary and technical expertise. Developing audiovisual patient information is an important area for nurses to be involved with. However, this must be performed within the context of the multiprofessional team. Teamworking, including patient involvement, is crucial as a wide variety of expertise is required. Many aspects of the process are transferable and will provide information and guidance for nurses, regardless of specialty, considering developing this format of patient information.

Iranian Effective Clinical Nurse Instructor evaluation tool: Development and psychometric testing

PubMed Central

Shahsavari, Hooman; Yekta, Zohreh Parsa; Zare, Zahra; Sigaroodi, Abdolhossain Emami

2014-01-01

Background: Clinical education is the heart of the nursing education program. Effective nursing clinical instructors are needed for graduating the future qualified nurses. There is a well-developed body of knowledge about the effectiveness of clinical teaching and the instructors. However, translating this knowledge into a context-based evaluation tool for measuring the effectiveness of Iranian clinical nursing instructors remains a deficiency. The purpose of this study is to describe the development and psychometric testing process of an instrument to evaluate the characteristics of Iranian effective clinical nurse instructor. Materials and Methods: Following a precise review of Iranian literatures and expert consultation, 83 statements about the characteristics that make clinical nurse instructors effective were extracted. In the next phase, the psychometric properties of the instrument were established by looking at the content validity, face validity, and internal consistency. Content validity of the instrument was assessed based on the comments of an expert panel including 10 nursing faculty members. During this phase, 30 items of the instrument were omitted or merged. Face validity of the instrument was assured based on the advices of 10 nursing students and 10 nursing faculty members. Finally, in the pilot test, the data of 168 filled questionnaires were gathered and analyzed by an exploratory factor analysis to reduce the items and identify the factor structure of the instrument. Results: Through subsequent analyses, of the 83 items, 31 items were merged or omitted. At last, 52 retained items were divided into four subscales including student-centric behaviors, clinical performances, planning ability, and personality traits. The Cronbach's alpha level of the inventory was 0.96, with the value for each domain ranging from 0.87 to 0.94. Conclusions: Iranian Effective Clinical Nurse Instructor evaluation tool has acceptable psychometric properties and can be used in evaluating the effectiveness of clinical nursing instructors. PMID:24834081

Trial endpoints for drug approval in oncology: Chemoprevention.

PubMed

Beitz, J

2001-04-01

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

Guidelines for Guidelines: Are They Up to the Task? A Comparative Assessment of Clinical Practice Guideline Development Handbooks

PubMed Central

Ansari, Shabnam; Rashidian, Arash

2012-01-01

Objectives We conducted a comparative review of clinical practice guideline development handbooks. We aimed to identify the main guideline development tasks, assign weights to the importance of each task using expert opinions and identify the handbooks that provided a comprehensive coverage of the tasks. Methods We systematically searched and included handbooks published (in English language) by national, international or professional bodies responsible for evidenced-based guideline development. We reviewed the handbooks to identify the main guideline development tasks and scored each handbook for each task from 0 (the handbook did not mention the task) to 2 (the task suitably addressed and explained), and calculated a weighted score for each handbook. The tasks included in over 75% of the handbooks were considered as ‘necessary’ tasks. Result Nineteen guideline development handbooks and twenty seven main tasks were identified. The guideline handbooks’ weighted scores ranged from 100 to 220. Four handbooks scored over 80% of the maximum possible score, developed by the National Institute for Health and Clinical Excellence, Swiss Centre for International Health, Scottish Intercollegiate Guidelines Network and World Health Organization. Necessary tasks were: selecting the guideline topic, determining the guideline scope, identifying relevant existing guidelines, involving the consumers, forming guideline development group,, developing clinical questions, systematic search for evidence, selecting relevant evidence, appraising identifies research evidence, making group decision, grading available evidence, creating recommendations, final stakeholder consultation, guideline implementation strategies, updating recommendations and correcting potential errors. Discussion Adequate details for evidence based development of guidelines were still lacking from many handbooks. The tasks relevant to ethical issues and piloting were missing in most handbooks. The findings help decision makers in identifying the necessary tasks for guideline development, provide an updated comparative list of guideline development handbooks, and provide a checklist to assess the comprehensiveness of guideline development processes. PMID:23189167

Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest

PubMed Central

2012-01-01

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development. PMID:22762776

Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest.

PubMed

Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul; Schünemann, Holger J; Woolf, Steven

2012-07-04

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development.

Innovations in Technology for the Treatment of Diabetes: Clinical Development of the Artificial Pancreas (an Autonomous System)

PubMed Central

Klonoff, David C; Zimliki, Charles L; Stevens, LCDR Alan; Beaston, Patricia; Pinkos, Arleen; Choe, Sally Y; Arreaza-Rubín, Guillermo; Heetderks, William

2011-01-01

The Food and Drug Administration in collaboration with the National Institutes of Health presented a public workshop to facilitate medical device innovation in the development of the artificial pancreas (or autonomous system) for the treatment of diabetes mellitus on November 10, 2010 in Gaithersburg, Maryland. The purpose of the workshop was to discuss four aspects of artificial pancreas research and development, including: (1) the current state of device systems for autonomous systems for the treatment of diabetes mellitus; (2) challenges in developing this expert device system using existing technology; (3) clinical expectations for these systems; and (4) development plans for the transition of this device system toward an outpatient setting. The patients discussed how clinical science, system components, and regulatory policies will all need to harmonize in order to achieve the goal of seeing an AP product brought forward to the marketplace for patients to use. PMID:21722597

Current trends in the clinical development of peptide therapeutics.

PubMed

Saladin, Pauline M; Zhang, Bodi D; Reichert, Janice M

2009-12-01

The development of peptides as drugs is attracting increasing attention from the pharmaceutical industry. This interest is at least partially a consequence of the widespread acceptance of therapeutic proteins by physicians and patients, and because of improvements to problems such as a short half-life and delivery issues. The markets for peptide-based compounds can be substantial, with six peptide drugs attaining global sales of more than US $750 million in 2008. To track trends in the clinical development and marketing approval of peptides, Tufts Center for the Study of Drug Development and Ferring Research Institute compiled publically available data for peptides that entered clinical trials sponsored by commercial firms, with a focus on peptide therapeutics, but also including peptide vaccines and diagnostics. The results provide an historical overview of the development of peptide therapeutics, and may inform strategic planning in this area.

Clinical EPR: Unique Opportunities and Some Challenges

PubMed Central

Swartz, Harold M.; Williams, Benjamin B.; Zaki, Bassem I.; Hartford, Alan C.; Jarvis, Lesley A.; Chen, Eunice; Comi, Richard J.; Ernstoff, Marc S.; Hou, Huagang; Khan, Nadeem; Swarts, Steven G.; Flood, Ann B.; Kuppusamy, Periannan

2014-01-01

Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe and regulatory constraints. This paper describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry), and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease, by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice. PMID:24439333

A course designed for undergraduate biochemistry students to learn about cultural diversity issues.

PubMed

Benore-Parsons, Marilee

2006-09-01

Biology, biochemistry, and other science students are well trained in science and familiar with how to conduct and evaluate scientific experiments. They are less aware of cultural issues or how these will impact their careers in research, education, or as professional health care workers. A course was developed for advanced undergraduate science majors to learn about diversity issues in a context that would be relevant to them, entitled "Diversity Issues in Health Care: Treatment and Research." Learning objectives included: developing awareness of current topics concerning diversity issues in health care; learning how research is carried out in health care, including pharmaceutical research, clinical trials, and social research; and learning about health care practices. Lectures and projects included readings on laboratory and clinical research, as well as literature on legal, race, gender, language, age, and income issues in health care research and clinical practice. Exams, papers, and a service learning project were used to determine the final course grade. Assessment indicated student understanding of diversity issues was improved, and the material was relevant. Copyright © 2006 International Union of Biochemistry and Molecular Biology, Inc.

Priorities for CMV vaccine development

PubMed Central

Krause, Philip R.; Bialek, Stephanie R.; Boppana, Suresh B.; Griffiths, Paul D.; Laughlin, Catherine A.; Ljungman, Per; Mocarski, Edward S.; Pass, Robert F.; Read, Jennifer S.; Schleiss, Mark R.; Plotkin, Stanley A.

2015-01-01

A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering preemptive antiviral therapy as an endpoint, because widespread use of preemptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection. PMID:24129123

Improving clinical and translational research training: a qualitative evaluation of the Atlanta Clinical and Translational Science Institute KL2-mentored research scholars program

PubMed Central

Comeau, Dawn L; Escoffery, Cam; Freedman, Ariela; Ziegler, Thomas R; Blumberg, Henry M

2017-01-01

A major impediment to improving the health of communities is the lack of qualified clinical and translational research (CTR) investigators. To address this workforce shortage, the National Institutes of Health (NIH) developed mechanisms to enhance the career development of CTR physician, PhD, and other doctoral junior faculty scientists including the CTR-focused K12 program and, subsequently, the KL2-mentored CTR career development program supported through the Clinical and Translational Science Awards (CTSAs). Our evaluation explores the impact of the K12/KL2 program embedded within the Atlanta Clinical and Translational Science Institute (ACTSI), a consortium linking Emory University, Morehouse School of Medicine and the Georgia Institute of Technology. We conducted qualitative interviews with program participants to evaluate the impact of the program on career development and collected data on traditional metrics (number of grants, publications). 46 combined K12/KL2 scholars were supported between 2002 and 2016. 30 (65%) of the 46 K12/KL2 scholars are women; 24 (52%) of the trainees are minorities, including 10 (22%) scholars who are members of an underrepresented minority group. Scholars reported increased research skills, strong mentorship experiences, and positive impact on their career trajectory. Among the 43 scholars who have completed the program, 39 (91%) remain engaged in CTR and received over $89 000 000 as principal investigators on federally funded awards. The K12/KL2 funding provided the training and protected time for successful career development of CTR scientists. These data highlight the need for continued support for CTR training programs for junior faculty. PMID:27591319

Integrated radiologist's workstation enabling the radiologist as an effective clinical consultant

NASA Astrophysics Data System (ADS)

McEnery, Kevin W.; Suitor, Charles T.; Hildebrand, Stan; Downs, Rebecca; Thompson, Stephen K.; Shepard, S. Jeff

2002-05-01

Since February 2000, radiologists at the M. D. Anderson Cancer Center have accessed clinical information through an internally developed radiologist's clinical interpretation workstation called RadStation. This project provides a fully integrated digital dictation workstation with clinical data review. RadStation enables the radiologist as an effective clinical consultant with access to pertinent sources of clinical information at the time of dictation. Data sources not only include prior radiology reports from the radiology information system (RIS) but access to pathology data, laboratory data, history and physicals, clinic notes, and operative reports. With integrated clinical information access, a radiologists's interpretation not only comments on morphologic findings but also can enable evaluation of study findings in the context of pertinent clinical presentation and history. Image access is enabled through the integration of an enterprise image archive (Stentor, San Francisco). Database integration is achieved by a combination of real time HL7 messaging and queries to SQL-based legacy databases. A three-tier system architecture accommodates expanding access to additional databases including real-time patient schedule as well as patient medications and allergies.

[The use of systematic review to develop a self-management program for CKD].

PubMed

Lee, Yu-Chin; Wu, Shu-Fang Vivienne; Lee, Mei-Chen; Chen, Fu-An; Yao, Yen-Hong; Wang, Chin-Ling

2014-12-01

Chronic kidney disease (CKD) has become a public health issue of international concern due to its high prevalence. The concept of self-management has been comprehensively applied in education programs that address chronic diseases. In recent years, many studies have used self-management programs in CKD interventions and have investigated the pre- and post-intervention physiological and psychological effectiveness of this approach. However, a complete clinical application program in the self-management model has yet to be developed for use in clinical renal care settings. A systematic review is used to develop a self-management program for CKD. Three implementation steps were used in this study. These steps include: (1) A systematic literature search and review using databases including CEPS (Chinese Electronic Periodical Services) of Airiti, National Digital Library of Theses and Dissertations in Taiwan, CINAHL, Pubmed, Medline, Cochrane Library, and Joanna Briggs Institute. A total of 22 studies were identified as valid and submitted to rigorous analysis. Of these, 4 were systematic literature reviews, 10 were randomized experimental studies, and 8 were non-randomized experimental studies. (2) Empirical evidence then was used to draft relevant guidelines on clinical application. (3) Finally, expert panels tested the validity of the draft to ensure the final version was valid for application in practice. This study designed a self-management program for CKD based on the findings of empirical studies. The content of this program included: design principles, categories, elements, and the intervention measures used in the self-management program. This program and then was assessed using the content validity index (CVI) and a four-point Liker's scale. The content validity score was .98. The guideline of self-management program to CKD was thus developed. This study developed a self-management program applicable to local care of CKD. It is hoped that the guidelines developed in this study offer a reference for clinical caregivers to improve their healthcare practices.

Drug discovery and development for rare genetic disorders.

PubMed

Sun, Wei; Zheng, Wei; Simeonov, Anton

2017-09-01

Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated. © 2017 Wiley Periodicals, Inc.

Identifying psychotic defenses in a clinical interview.

PubMed

Berney, Sylvie; de Roten, Yves; Beretta, Véronique; Kramer, Ueli; Despland, Jean-Nicolas

2014-05-01

The Defense Mechanisms Rating Scales (DMRS), one of the most widely used and validated instruments in the study of defense mechanisms, does not include psychotic defenses. The Psychotic-DMRS (P-DMRS) has been developed to include 6 psychotic defense mechanisms: psychotic denial, autistic withdrawal, distortion, delusional projection, fragmentation, and concretization. We discuss psychotic defenses, including the difference between psychotic defenses and psychotic symptoms. Six clinical illustrations demonstrate how the 6 P-DMRS defenses can be identified in patients' narratives selected from the transcripts of dynamic interviews. Implications with respect to patient evaluation and treatment are discussed. © 2014 Wiley Periodicals, Inc.

Clinical nurse specialists as entrepreneurs: constrained or liberated.

PubMed

Austin, Lynn; Luker, Karen; Roland, Martin; Ronald, Martin

2006-12-01

This qualitative study explored the experiences of two groups of clinical nurse specialists--continence advisors and tissue viability nurses--working in primary care in the UK. In particular, the study focused on how clinical nurse specialists' relationships with other health-care professionals had an impact on their role. Clinical nurse specialists are recognized worldwide as having expertise in a given field, which they use to develop the practice of others. Additionally, clinical nurse specialists share many of the characteristics of entrepreneurs, which they use to develop services related to their speciality. However, little research has been conducted in relation to clinical nurse specialists' experiences as they attempt to diversify nursing practice. An ethnographic approach was adopted comprising many elements of Glaserian grounded theory. Data were collected via participant observation and face-to-face interviews with 22 clinical nurse specialists. Services provided by clinical nurse specialists were not static, clinical nurse specialists being the main drivers for service developments. However, clinical nurse specialists encountered difficulties when introducing new ideas. Given their role as advisors, clinical nurse specialists lacked authority to bring about change and were dependent on a number of mechanisms to bring about change, including 'cultivating relationships' with more powerful others, most notably the speciality consultant. The UK government has pledged to 'liberate the talents of nurses' so that their skills can be used to progress patient services. This study highlights the fact that a lack of collaborative working practices between health-care professionals led to clinical nurse specialists being constrained. Health-care organizations need to provide an environment in which the entrepreneurial skills of clinical nurse specialists may be capitalized on. In the absence of an outlet for their ideas regarding service developments, clinical nurse specialists may remain dependent on the mechanisms witnessed in this study for some time.

Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: challenges and opportunities.

PubMed

Dasari, Vijayendra; Bhatt, Kunal H; Smith, Corey; Khanna, Rajiv

2017-04-01

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a number of clinical manifestations. Primary EBV infection in young adolescents often manifests as acute infectious mononucleosis and latent infection is associated with multiple lymphoid and epithelial cancers and autoimmune disorders, particularly multiple sclerosis. Areas covered: Over the last decade, our understanding of pathogenesis and immune regulation of EBV-associated diseases has provided an important platform for the development of novel vaccine formulations. In this review, we discuss developmental strategies for prophylactic and therapeutic EBV vaccines which have been assessed in preclinical and clinical settings. Expert commentary: Major roadblocks in EBV vaccine development include no precise understanding of the clinical correlates of protection, uncertainty about adjuvant selection and the unavailability of appropriate animal models. Recent development of new EBV vaccine formulations provides exciting opportunities for the formal clinical assessment of novel formulations.

Assessing Interprofessional education in a student-faculty collaborative practice network.

PubMed

Young, Grace J; Cohen, Marya J; Blanchfield, Bonnie B; Jones, Meissa M; Reidy, Patricia A; Weinstein, Amy R

2017-07-01

Although interprofessional relationships are ubiquitous in clinical practice, undergraduate medical students have limited opportunities to develop these relationships in the clinical setting. A few student-faculty collaborative practice networks (SFCPNs) have been working to address this issue, but limited data exist examining the nature and extent of these practices. A systematic survey at a Harvard-affiliated SFCPN is utilised to evaluate the quantity and quality of interprofessional interactions, isolate improvements, and identify challenges in undergraduate interprofessional education (IPE). Our data corroborate previous findings in which interprofessional clinical learning was shown to have positive effects on student development and align with all four domains of Interprofessional Education Collaborative core competencies, including interprofessional ethics and values, roles and responsibilities, interprofessional communication, and teams and teamwork. These results highlight the unique opportunity and growing necessity of integrating IPE in SFCPNs to endorse the development of collaborative and professional competencies in clinical modalities of patient care.

Development of questionnaires to measure patient preferences for intranasal corticosteroids in patients with allergic rhinitis.

PubMed

Meltzer, Eli O; Hadley, James; Blaiss, Michael; Benninger, Michael; Kimel, Miriam; Kleinman, Leah; Dupclay, Leon; Garcia, Jorge; Leahy, Michael; Georges, George

2005-02-01

To develop a questionnaire to evaluate preferences for attributes of intranasal corticosteroids (INSs) in clinical trials with allergic rhinitis (AR) patients. Established questionnaire development practices were used, including performance of a literature review and use of patient and physician focus groups, cognitive debriefing interviews, and pilot testing before validation. Findings from patient and physician focus groups suggest that sensory attributes are relevant to AR patients when choosing INSs. Physician focus groups identified the need for 2 distinct preference instruments, a clinical trial patient preference questionnaire (CTPPQ) and a clinical practice preference questionnaire (CPPPQ). A pilot study suggests that the CTPPQ is capable of discriminating between 2 INSs in the clinical trial setting. Initial findings suggest that items in the CTPPQ and CPPPQ are easy to understand and relevant to patients. Further validation studies with larger sample sizes are needed to assess the psychometric properties of both questionnaires. B-20.

Clinical aspects of the Mayo/IBM PACS project

NASA Astrophysics Data System (ADS)

Forbes, Glenn S.; Morin, Richard L.; Pavlicek, William

1991-07-01

A joint project between Mayo Clinic and IBM to develop a picture archival and communications system has been under development for three years. This project began as a potential solution to a pressing archival problem in magnetic resonance imaging. The project has grown to encompass a much larger sphere of activity including workstations, image retrieval, and report archival. This report focuses on the clinical aspects involved in the design, development, and implementation of such a system. In particular, emphasis is placed on the clinical impact of the system both inside and outside of the radiology department. The primary concerns have centered on fidelity of archival data, ease of use, and diagnostic efficacy. The project to date has been limited to neuroradiology practice. This group consists of nine staff radiologists and fellows. Administrative policy decisions regarding the accessibility and available of digital data in the clinical environment have been much more difficult and complex than originally conceived. Based on the observations thus far, the authors believe the system will become a useful and valuable adjunct to clinical practice of radiology.

The chemical evolution of oligonucleotide therapies of clinical utility

PubMed Central

Khvorova, Anastasia; Watts, Jonathan K.

2017-01-01

After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency properties are derived primarily from the chemical structure of the oligonucleotide, while their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design demonstrate appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized as a whole, using a combination of sugar, backbone, nucleobase and 3′/5′-terminal modifications. A portfolio of chemistries can be used to confer drug like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. Outstanding challenges in oligonucleotide chemical development include optimization of chemical architectures to ensure long-term safety and to enable robust clinical activity beyond the liver. PMID:28244990

Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis: a systematic review.

PubMed

Bonnett, Laura Jayne; Ken-Dror, Gie; Davies, Geraint Rhys

2018-02-21

Despite more than 60 years of clinical trials, tuberculosis (TB) still causes a high global burden of mortality and morbidity. Treatment currently requires multiple drugs in combination, taken over a prolonged period. New drugs are needed to shorten treatment duration, prevent resistance and reduce adverse events. However, to improve on current methodology in drug development, a more complete understanding of the existing clinical evidence base is required. A systematic review was undertaken to summarise outcomes reported in phase III trials of patients with newly diagnosed pulmonary TB. A systematic search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Of 248 included studies, 229 considered "on-treatment" outcomes whilst 148 reported "off-treatment" outcomes. There was wide variation and ambiguity in the definition of reported outcomes, including their relationship to treatment and in the time points evaluated. Additional challenges were observed regarding the analysis approach taken (per protocol versus intention to treat) and the varying durations of "intensive" and "continuation" phases of treatment. Bacteriological outcomes were most frequently reported but radiological and clinical data were often included as an implicit or explicit component of the overall definition of outcome. Terminology used to define long-term outcomes in phase III trials is inconsistent, reflecting evolving differences in protocols and practices. For successful future cumulative meta-analysis, the findings of this review suggest that greater availability of individual patient data and the development of a core outcome set would be desirable. In the meantime, we propose a simple and logical approach which should facilitate combination of key evidence and inform improvements in the methodology of TB drug development and clinical trials.

Developing a tool to measure pharmacoeconomic outcomes of post-surgical pain management interventions.

PubMed

Keller, Deborah S; Smalarz, Amy; Haas, Eric M

2016-01-01

Financial pressures have limited the ability of providers to use medication that may improve clinical outcomes and patient satisfaction. New interventions are often fraught with resistance from individual cost centers. A value realization tool (VRT) is essential for separate cost centers to communicate and comprehend the overall financial and clinical implications of post-surgical pain management medication interventions (PSMI). The goal was to describe development of a VRT. An evaluation of common in-patient PSMI approaches, impacts, and costs was performed. A multidisciplinary task force guided development of the VRT to ensure appropriate representation and relevance to clinical practice. The main outcome was an Excel-based tool that communicates the overall cost/benefit of PSMI for the post-operative patient encounter. The VRT aggregated input data on costs, clinical impact, and nursing burden of PSMI assessment and monitoring into two high-level outcome reports: Overall Cost Impact and Nurse & Patient Impact. Costs included PSMI specific medication, equipment, professional placement, labor, overall/opioid-related adverse events, re-admissions, and length of stay. Nursing impact included level of practice interference, job satisfaction, and patient care metrics. Patient impact included pain scores, opioid use, PACU time, and satisfaction. Reference data was provided for individual institutions that may not collect all variables included in the VRT. The VRT is a valuable way for administrators to assess PSMI cost/benefits and for individual cost centers to see the overall value of individual interventions. The user-friendly, decision-support tool allows the end-user to use built-in referenced or personalized outcome data, increasing relevance to their institutions. This broad picture could facilitate communication across cost centers and evidence-based decisions for appropriate use and impacts of PSMI.

Current Progress of siRNA/shRNA Therapeutics in Clinical Trials

PubMed Central

Burnett, John C.; Rossi, John J.; Tiemann, Katrin

2012-01-01

Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. For some of the drugs, advancements in bioengineering and nanotechnology have led to improved control of delivery and release of the siRNA. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases. PMID:21744502

Consumer attitudes towards the establishment of a national Australian familial cancer research database by the Inherited Cancer Connect (ICCon) Partnership.

PubMed

Forrest, Laura; Mitchell, Gillian; Thrupp, Letitia; Petelin, Lara; Richardson, Kate; Mascarenhas, Lyon; Young, Mary-Anne

2018-01-01

Clinical genetics units hold large amounts of information which could be utilised to benefit patients and their families. In Australia, a national research database, the Inherited Cancer Connect (ICCon) database, is being established that comprises clinical genetic data held for all carriers of mutations in cancer predisposition genes. Consumer input was sought to establish the acceptability of the inclusion of clinical genetic data into a research database. A qualitative approach using a modified nominal group technique was used to collect data through consumer forums conducted in three Australian states. Individuals who had previously received care from Familial Cancer Centres were invited to participate. Twenty-four consumers participated in three forums. Participants expressed positive attitudes about the establishment of the ICCon database, which were informed by the perceived benefits of the database including improved health outcomes for individuals with inherited cancer syndromes. Most participants were comfortable to waive consent for their clinical information to be included in the research database in a de-identified format. As major stakeholders, consumers have an integral role in contributing to the development and conduct of the ICCon database. As an initial step in the development of the ICCon database, the forums demonstrated consumers' acceptance of important aspects of the database including waiver of consent.

Current progress of siRNA/shRNA therapeutics in clinical trials.

PubMed

Burnett, John C; Rossi, John J; Tiemann, Katrin

2011-09-01

Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers, including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. Advancements in bioengineering and nanotechnology have led to improved control of delivery and release of some siRNA therapeutics. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of replication-deficient adenovirus malaria vaccines.

PubMed

Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

2017-03-01

Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

Identifying viable regulatory and innovation pathways for regenerative medicine: a case study of cultured red blood cells.

PubMed

Mittra, J; Tait, J; Mastroeni, M; Turner, M L; Mountford, J C; Bruce, K

2015-01-25

The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5-10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Herbal medicine development: a plea for a rigorous scientific foundation.

PubMed

Lietman, Paul S

2012-09-01

Science, including rigorous basic scientific research and rigorous clinical research, must underlie both the development and the clinical use of herbal medicines. Yet almost none of the hundreds or thousands of articles that are published each year on some aspect of herbal medicines, adheres to 3 simple but profound scientific principles must underlie all of herbal drug development or clinical use. Three fundamental principles that should underlie everyone's thinking about the development and/or clinical use of any herbal medicine. (1) There must be standardization and regulation (rigorously enforced) of the product being studied or being used clinically. (2) There must be scientific proof of a beneficial clinical effect for something of value to the patient and established by rigorous clinical research. (3) There must be scientific proof of safety (acceptable toxicity) for the patient and established by rigorous clinical research. These fundamental principles of science have ramifications for both the scientist and the clinician. It is critically important that both the investigator and the prescriber know exactly what is in the studied or recommended product and how effective and toxic it is. We will find new and useful drugs from natural sources. However, we will have to learn how to study herbal medicines rigorously, and we will have to try to convince the believers in herbal medicines of the wisdom and even the necessity of a rigorous scientific approach to herbal medicine development. Both biomedical science and practicing physicians must enthusiastically accept the responsibility for searching for truth in the discovery and development of new herbal medicines, in the truthful teaching about herbal medicines from a scientific perspective, and in the scientifically proven clinical use of herbal medicines.

Implementation of an intraoperative clinical experience for senior level baccalaureate nursing students.

PubMed

Mott, Jason

2012-04-01

Perioperative nursing is a specialty that has been eliminated from many nursing education programs. With the loss of perioperative clinical experiences, the number of students pursuing a career in perioperative nursing after graduation has declined. A faculty member at one Midwestern school of nursing developed and implemented a perioperative clinical experience for senior-level baccalaureate nursing students in a critical care nursing course. This program, developed with the assistance of four local hospitals and the college of nursing, included an eight-hour OR orientation and 56 clinical hours. Students were placed in the OR under preceptor guidance and supervision. Feedback from evaluations was positive and provided recommendations for improving the program, in particular, to allow more clinical hours and more hands-on experience for the students. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

A Methodology for Validating Safety Heuristics Using Clinical Simulations: Identifying and Preventing Possible Technology-Induced Errors Related to Using Health Information Systems

PubMed Central

Borycki, Elizabeth; Kushniruk, Andre; Carvalho, Christopher

2013-01-01

Internationally, health information systems (HIS) safety has emerged as a significant concern for governments. Recently, research has emerged that has documented the ability of HIS to be implicated in the harm and death of patients. Researchers have attempted to develop methods that can be used to prevent or reduce technology-induced errors. Some researchers are developing methods that can be employed prior to systems release. These methods include the development of safety heuristics and clinical simulations. In this paper, we outline our methodology for developing safety heuristics specific to identifying the features or functions of a HIS user interface design that may lead to technology-induced errors. We follow this with a description of a methodological approach to validate these heuristics using clinical simulations. PMID:23606902

Recent developments of cyclotron produced radionuclides for nuclear cardiology

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Jansen, D. E.; Corbett, J. R.

1987-04-01

For over a decade myocardial perfusion imaging with thallium-201, a cyclotron product, has been routinely used in clinical medicine. Recent advances have allowed the efficient production of very high purity (> 99.8%) iodine-123. New metabolically active 123I labeled radiopharmaceuticals, including alkyl and phenyl fatty acids, and norepinephrine analogs, have been developed and are undergoing clinical trials. Fab' fragments of monoclonal antibodies to cardiac myosin have been labeled with indium-111 ( 111In) and are undergoing clinical evaluation for imaging myocardial infarcts. Monoclonal antibodies to platelets, fibrin, and the thrombolytic agent, tissue plasminogen activator (TPA), have recently been labeled with 111In. Together these developments in radiotracers and instrumentation should have a significant impact on the future of cardiovascular nuclear medicine. This manuscript will discuss developments in single photon emitting radiotracers for myocardial imaging.

Clinical associations of maternal thyroid function with foetal brain development: Epidemiological interpretation and overview of available evidence.

PubMed

Korevaar, Tim I M; Tiemeier, Henning; Peeters, Robin P

2018-04-24

Thyroid hormone is an important regulator of early brain development, particularly during early stages of gestation during which foetal thyroid hormone availability depends on the maternal transfer of thyroid hormones. There is a wide range of experimental studies showing that low maternal thyroid hormone availability is associated with suboptimal brain development parameters. While few clinical studies have shown that overt maternal hypothyroidism is associated with lower child IQ, the question whether more subclinical changes in maternal thyroid function could also lead to suboptimal foetal brain development. In this review, we put the latter studies in perspective and discuss their interpretation from an epidemiological and clinical perspective. Furthermore, we extend this discussion to also include future perspective and identify important knowledge gaps in the field. © 2018 John Wiley & Sons Ltd.

Development, implementation and evaluation of a clinical research engagement and leadership capacity building program in a large Australian health care service.

PubMed

Misso, Marie L; Ilic, Dragan; Haines, Terry P; Hutchinson, Alison M; East, Christine E; Teede, Helena J

2016-01-14

Health professionals need to be integrated more effectively in clinical research to ensure that research addresses clinical needs and provides practical solutions at the coal face of care. In light of limited evidence on how best to achieve this, evaluation of strategies to introduce, adapt and sustain evidence-based practices across different populations and settings is required. This project aims to address this gap through the co-design, development, implementation, evaluation, refinement and ultimately scale-up of a clinical research engagement and leadership capacity building program in a clinical setting with little to no co-ordinated approach to clinical research engagement and education. The protocol is based on principles of research capacity building and on a six-step framework, which have previously led to successful implementation and long-term sustainability. A mixed methods study design will be used. Methods will include: (1) a review of the literature about strategies that engage health professionals in research through capacity building and/or education in research methods; (2) a review of existing local research education and support elements; (3) a needs assessment in the local clinical setting, including an online cross-sectional survey and semi-structured interviews; (4) co-design and development of an educational and support program; (5) implementation of the program in the clinical environment; and (6) pre- and post-implementation evaluation and ultimately program scale-up. The evaluation focuses on research activity and knowledge, attitudes and preferences about clinical research, evidence-based practice and leadership and post implementation, about their satisfaction with the program. The investigators will evaluate the feasibility and effect of the program according to capacity building measures and will revise where appropriate prior to scale-up. It is anticipated that this clinical research engagement and leadership capacity building program will enable and enhance clinically relevant research to be led and conducted by health professionals in the health setting. This approach will also encourage identification of areas of clinical uncertainty and need that can be addressed through clinical research within the health setting.

Evaluation through research of a three-track career ladder program for registered nurses.

PubMed

Korman, Carol; Eliades, Aris Beoglos

2010-01-01

A descriptive study design was employed to survey registered nurse participants in a career ladder program comprising of three tracks: clinical, education, and management. Findings indicate that participation allows nurses of varying education preparation and roles to demonstrate professional development. Implications for staff development include efficacy of the online survey technique, provision of a reliable tool to evaluate a career ladder, and evaluation of a career ladder that includes the staff development educator.

Application of a contextual instructional framework in a continuing professional development training program for physiotherapists in Rwanda.

PubMed

Dunleavy, Kim; Chevan, Julia; Sander, Antoinette P; Gasherebuka, Jean Damascene; Mann, Monika

2018-06-01

Continuing professional development is an important component of capacity building in low resource countries. The purpose of this case study is to describe the use of a contextual instructional framework to guide the processes and instructional design choices for a series of continuing professional development courses for physiotherapists in Rwanda. Four phases of the project are described: (1) program proposal, needs assessment and planning, (2) organization of the program and instructional design, (3) instructional delivery and (4) evaluation. Contextual facilitating factors and needs informed choices in each phase. The model resulted in delivery of continuing professional development to the majority of physiotherapists in Rwanda (n = 168, 0.48 rural/0.52 urban) with participants reporting improvement in skills and perceived benefit for their patients. Environmental and healthcare system factors resulted in offering the courses in rural and urban areas. Content was developed and delivered in partnership with Rwandan coinstructors. Based on the domestic needs identified in early courses, the program included advocacy and leadership activities, in addition to practical and clinical instruction. The contextual factors (environment, healthcare service organization, need for rehabilitation and status and history of the physiotherapy profession) were essential for project and instructional choices. Facilitating factors included the established professional degree and association, continuing professional development requirements, a core group of active professionals and an existing foundation from other projects. The processes and contextual considerations may be useful in countries with established professional-level education but without established postentry-level training. Implications for Rehabilitation Organizations planning continuing professional development programs may benefit from considering the context surrounding training when planning, designing and developing instruction. The surrounding context including the environment, the organization of healthcare services, the population defined need for rehabilitation, and the domestic status and history of the physiotherapy profession, is important for physiotherapy projects in countries with lower resources. Facilitating factors in low resource countries such as an established professional degree and association, continuing professional development requirements, a core group of active professionals and an existing foundation from other projects impact the success of projects. Methods that may be useful for relevance, dissemination and consistency include involvement of in-country leaders and instructors and attendance in multiple courses with consistent themes. Rehabilitation professionals in low resource countries may benefit from continuing professional development courses that emphasize practical skills, and clinical reasoning, accompanied by clinical mentoring and directed coaching that encourages knowledge transfer to the clinical setting. Active learning approaches and multiple progressive courses provide opportunities to develop peer support through professional communities of practice.

Implementation of Epic Beaker Clinical Pathology at Stanford University Medical Center.

PubMed

Tan, Brent T; Fralick, Jennifer; Flores, William; Schrandt, Cary; Davis, Vicki; Bruynell, Tom; Wilson, Lisa; Christopher, John; Weber, Shirley; Shah, Neil

2017-03-01

To provide an account of implementation of the Epic Beaker 2014 clinical pathology module at Stanford University Medical Center and highlight strengths and weaknesses of the system. Based on a formal selection process, Stanford selected Epic Beaker to replace Sunquest as the clinical laboratory information system (LIS). The rationale included integration between the LIS and already installed Epic electronic medical record (EMR), reduction in the number of systems and interfaces, and positive patient identification (PPID). The build was significantly customized and included a first of its kind Epic-to-Epic interface. This was due to the clinical laboratory serving two hospitals (pediatric and adult) with independent instances of Epic. Test turnaround times showed improvement from historical baselines, mostly because of the implementation of PPID. PPID also resulted in significant reduction in mislabeled specimens. Epic 2014 Beaker clinical pathology is a viable LIS with adequate functionality for a large academic center. Strengths include PPID and integration with the EMR. Integration provides laboratory users with ready access to the patient's relevant clinical history to assist releasing of results and gives physician and nurse providers sophisticated add-on ordering and specimen collection workflows. Areas that could use further development include specimen aliquoting, quality control reporting, and maintenance tools. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

School Nurse Summer Institute: A Model for Professional Development

ERIC Educational Resources Information Center

Neighbors, Marianne; Barta, Kathleen

2004-01-01

The components of a professional development model designed to empower school nurses to become leaders in school health services is described. The model was implemented during a 3-day professional development institute that included clinical and leadership components, especially coalition building, with two follow-up sessions in the fall and…

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

PubMed Central

Tsutsumi, Lissa S.; Owusu, Yaw B.; Hurdle, Julian G.; Sun, Dianqing

2014-01-01

Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID:24236721

TRAINING IN THERAPEUTIC WORK WITH CHILDREN. CLINICAL APPROACHES TO PROBLEMS OF CHILDHOOD, VOLUME 2. LANGLEY PORTER CHILD PSYCHIATRY SERIES.

ERIC Educational Resources Information Center

BERLIN, I.N., ED.; SZUREK, S.A., ED.

THE COLLECTION CONTAINS LECTURES AND PAPERS BY VARIOUS AUTHORS DEALING WITH CHILD PSYCHOLOGY, CONSIDERATION OF CHILD PSYCHIATRY INCLUDES DEFINITION, PERSONALITY DEVELOPMENT, FACTORS IN CHILDREN'S PSYCHIATRIC DISORDERS, CLINICAL SYNDROMES, CHILDHOOD PSYCHOSES, AND PRINCIPLES OF PSYCHOTHERAPY. AN OVERVIEW OF A PHILOSOPHY OF PSYCHOTHERAPY IN CHILD…

Survey of Clinical Pharmacology Programs in U.S. and Canadian Medical Schools.

ERIC Educational Resources Information Center

And Others; Fisher, James W.

1980-01-01

A survey is reported that was undertaken by the Association for Medical School Pharmacology to assess the status of developing clinical pharmacology programs in medical schools in the United States and Canada and to determine why some schools have been unable to mount such programs. Survey questions are included. (Author/JMD)

Clinical Linguistics: Its Past, Present and Future

ERIC Educational Resources Information Center

Perkins, Michael R.

2011-01-01

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the…

Functional Analysis Identified Habit Reversal Components for the Treatment of Motor Tics

ERIC Educational Resources Information Center

Dufrene, Brad A.; Harpole, Lauren Lestremau; Sterling, Heather E.; Perry, Erin J.; Burton, Britney; Zoder-Martell, Kimberly

2013-01-01

This study included brief functional analyses and treatment for motor tics exhibited by two children with Tourette Syndrome. Brief functional analyses were conducted in an outpatient treatment center and results were used to develop individualized habit reversal procedures. Treatment data were collected in clinic for one child and in clinic and…

[Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China].

PubMed

2018-01-23

Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.

Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East.

PubMed

Al Sayed, Nasreen; Al Waili, Khalid; Alawadi, Fatheya; Al-Ghamdi, Saeed; Al Mahmeed, Wael; Al-Nouri, Fahad; Al Rukhaimi, Mona; Al-Rasadi, Khalid; Awan, Zuhier; Farghaly, Mohamed; Hassanein, Mohamed; Sabbour, Hani; Zubaid, Mohammad; Barter, Philip

2016-12-15

Plasma lipid disorders are key risk factors for the development of atherosclerotic cardiovascular disease (ASCVD) and are prevalent in the Middle East, with rates increasing in recent decades. Despite this, no region-specific guidelines for managing plasma lipids exist and there is a lack of use of guidelines developed in other regions. A multidisciplinary panel of regional experts was convened to develop consensus clinical recommendations for the management of plasma lipids in the Middle East. The panel considered existing international guidelines and regional clinical experience to develop recommendations. The panel's recommendations include plasma lipid screening, ASCVD risk calculation and treatment considerations. The panel recommend that plasma lipid levels should be measured in all at-risk patients and at regular intervals in all adults from the age of 20years. A scoring system should be used to calculate ASCVD risk that includes known lipid and non-lipid risk factors. Primary treatment targets include low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol. Lifestyle modifications should be first-line treatment for all patients; the first-line pharmacological treatment targeting plasma lipids in patients at moderate-to-high risk of ASCVD is statin therapy, with a number of adjunctive or second-line agents available. Guidance is also provided on the management of underlying conditions and special populations; of particular pertinence in the region are familial hypercholesterolaemia, diabetes and metabolic dyslipidaemia. These consensus clinical recommendations provide practicing clinicians with comprehensive, region-specific guidance to improve the detection and management of plasma lipid disorders in patients in the Middle East. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.

PubMed

McCann, Liza J; Pilkington, Clarissa A; Huber, Adam M; Ravelli, Angelo; Appelbe, Duncan; Kirkham, Jamie J; Williamson, Paula R; Aggarwal, Amita; Christopher-Stine, Lisa; Constantin, Tamas; Feldman, Brian M; Lundberg, Ingrid; Maillard, Sue; Mathiesen, Pernille; Murphy, Ruth; Pachman, Lauren M; Reed, Ann M; Rider, Lisa G; van Royen-Kerkof, Annet; Russo, Ricardo; Spinty, Stefan; Wedderburn, Lucy R; Beresford, Michael W

2018-02-01

This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres. A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation. A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter. Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Regulatory scientific advice in drug development: does company size make a difference?

PubMed Central

Putzeist, Michelle; Gispen-De Wied, Christine C.; Hoes, Arno W.; Leufkens, Hubert G.

2010-01-01

Purpose To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. Methodology A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006–2008. Definition of company size was based on ranking by total revenues (Scrip’s Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). Results In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P < 0.001) and clinical questions less frequently than large companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P < 0.001). Conclusion The array of topics addressed in SA provides an interesting outlook on what industry considers to be still unresolved in drug development and worthwhile to discuss with regulators. Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development. PMID:21049297

Regulatory scientific advice in drug development: does company size make a difference?

PubMed

Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Gispen-De Wied, Christine C; Hoes, Arno W; Leufkens, Hubert G

2011-02-01

To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006-2008. Definition of company size was based on ranking by total revenues (Scrip's Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P < 0.001) and clinical questions less frequently than large companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P < 0.001). The array of topics addressed in SA provides an interesting outlook on what industry considers to be still unresolved in drug development and worthwhile to discuss with regulators. Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development.

v3NLP Framework: Tools to Build Applications for Extracting Concepts from Clinical Text

PubMed Central

Divita, Guy; Carter, Marjorie E.; Tran, Le-Thuy; Redd, Doug; Zeng, Qing T; Duvall, Scott; Samore, Matthew H.; Gundlapalli, Adi V.

2016-01-01

Introduction: Substantial amounts of clinically significant information are contained only within the narrative of the clinical notes in electronic medical records. The v3NLP Framework is a set of “best-of-breed” functionalities developed to transform this information into structured data for use in quality improvement, research, population health surveillance, and decision support. Background: MetaMap, cTAKES and similar well-known natural language processing (NLP) tools do not have sufficient scalability out of the box. The v3NLP Framework evolved out of the necessity to scale-up these tools up and provide a framework to customize and tune techniques that fit a variety of tasks, including document classification, tuned concept extraction for specific conditions, patient classification, and information retrieval. Innovation: Beyond scalability, several v3NLP Framework-developed projects have been efficacy tested and benchmarked. While v3NLP Framework includes annotators, pipelines and applications, its functionalities enable developers to create novel annotators and to place annotators into pipelines and scaled applications. Discussion: The v3NLP Framework has been successfully utilized in many projects including general concept extraction, risk factors for homelessness among veterans, and identification of mentions of the presence of an indwelling urinary catheter. Projects as diverse as predicting colonization with methicillin-resistant Staphylococcus aureus and extracting references to military sexual trauma are being built using v3NLP Framework components. Conclusion: The v3NLP Framework is a set of functionalities and components that provide Java developers with the ability to create novel annotators and to place those annotators into pipelines and applications to extract concepts from clinical text. There are scale-up and scale-out functionalities to process large numbers of records. PMID:27683667

New developments in technology-assisted supervision and training: a practical overview.

PubMed

Rousmaniere, Tony; Abbass, Allan; Frederickson, Jon

2014-11-01

Clinical supervision and training are now widely available online. In this article, three of the most accessible and widely adopted new developments in clinical supervision and training technology are described: Videoconference supervision, cloud-based file sharing software, and clinical outcome tracking software. Partial transcripts from two online supervision sessions are provided as examples of videoconference-based supervision. The benefits and limitations of technology in supervision and training are discussed, with an emphasis on supervision process, ethics, privacy, and security. Recommendations for supervision practice are made, including methods to enhance experiential learning, the supervisory working alliance, and online security. © 2014 Wiley Periodicals, Inc.

Case study: physicians develop results viewer amid Y2K commotion.

PubMed

Wurz, J A; Manis, J L

2000-01-01

Amid a flurry of Y2K preparations, which included converting patient accounting and order processing systems for six of its eight hospitals, Advocate Health Care needed to address physician complaints that the compliant software was awkward. By partnering with physicians, information systems (IS) rapidly developed a solution that met both the need for compliance and the demand for an easy-to-use, patient-centric clinical information system. A robust, browser-based results viewer provides physician access to information from patient accounting, order processing, and several clinical ancillary systems. Advocate anticipates greater challenges as the system is promoted to other sites and clinical communities.

Best Practices in Stability Indicating Method Development and Validation for Non-clinical Dose Formulations.

PubMed

Henry, Teresa R; Penn, Lara D; Conerty, Jason R; Wright, Francesca E; Gorman, Gregory; Pack, Brian W

2016-11-01

Non-clinical dose formulations (also known as pre-clinical or GLP formulations) play a key role in early drug development. These formulations are used to introduce active pharmaceutical ingredients (APIs) into test organisms for both pharmacokinetic and toxicological studies. Since these studies are ultimately used to support dose and safety ranges in human studies, it is important to understand not only the concentration and PK/PD of the active ingredient but also to generate safety data for likely process impurities and degradation products of the active ingredient. As such, many in the industry have chosen to develop and validate methods which can accurately detect and quantify the active ingredient along with impurities and degradation products. Such methods often provide trendable results which are predictive of stability, thus leading to the name; stability indicating methods. This document provides an overview of best practices for those choosing to include development and validation of such methods as part of their non-clinical drug development program. This document is intended to support teams who are either new to stability indicating method development and validation or who are less familiar with the requirements of validation due to their position within the product development life cycle.

Critical role of ethics in clinical management and public health response to the West Africa Ebola epidemic.

PubMed

Folayan, Morenike O; Haire, Bridget G; Brown, Brandon

2016-01-01

The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis. These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak. Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries. The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development. In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions. Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups. The compassionate use of experimental drugs intersects both with research ethics and clinical care. The role of developed countries also came under scrutiny, and we concluded that developed countries have an obligation to contribute to the containment of EVD infection by contributing to the strengthening of local health care systems and infrastructure in an effort to provide fair benefits to communities engaged in research, ensuring that affected countries have ready and affordable access to any therapeutic or preventative interventions developed, and supporting affected countries on their way to recovery from the impact of EVD on their social and economic lives.

Development of a clinical pharmacy model within an Australian home nursing service using co-creation and participatory action research: the Visiting Pharmacist (ViP) study

PubMed Central

Lee, Cik Yin; Beanland, Christine; Goeman, Dianne P; Petrie, Neil; Petrie, Barbara; Vise, Felicity; Gray, June

2017-01-01

Objective To develop a collaborative, person-centred model of clinical pharmacy support for community nurses and their medication management clients. Design Co-creation and participatory action research, based on reflection, data collection, interaction and feedback from participants and other stakeholders. Setting A large, non-profit home nursing service in Melbourne, Australia. Participants Older people referred to the home nursing service for medication management, their carers, community nurses, general practitioners (GPs) and pharmacists, a multidisciplinary stakeholder reference group (including consumer representation) and the project team. Data collection and analysis Feedback and reflections from minutes, notes and transcripts from: project team meetings, clinical pharmacists’ reflective diaries and interviews, meetings with community nurses, reference group meetings and interviews and focus groups with 27 older people, 18 carers, 53 nurses, 15 GPs and seven community pharmacists. Results The model was based on best practice medication management standards and designed to address key medication management issues raised by stakeholders. Pharmacist roles included direct client care and indirect care. Direct care included home visits, medication reconciliation, medication review, medication regimen simplification, preparation of medication lists for clients and nurses, liaison and information sharing with prescribers and pharmacies and patient/carer education. Indirect care included providing medicines information and education for nurses and assisting with review and implementation of organisational medication policies and procedures. The model allowed nurses to refer directly to the pharmacist, enabling timely resolution of medication issues. Direct care was provided to 84 older people over a 15-month implementation period. Ongoing feedback and consultation, in line with participatory action research principles, informed the development and refinement of the model and identification of enablers and challenges. Conclusions A collaborative, person-centred clinical pharmacy model that addressed the needs of clients, carers, nurses and other stakeholders was successfully developed. The model is likely to have applicability to home nursing services nationally and internationally. PMID:29102998

AMS in drug development at GSK

NASA Astrophysics Data System (ADS)

Young, G. C.; Ellis, W. J.

2007-06-01

A history of the use of AMS in GSK studies spanning the last 8 years (1998-2005) is presented, including use in pilot studies through to clinical, animal and in vitro studies. A brief summary of the status of GSK's in-house AMS capability is outlined and views on the future of AMS in GSK are presented, including potential impact on drug development and potential advances in AMS technology.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?

PubMed

Hamaker, M E; Stauder, R; van Munster, B C

2014-03-01

Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.

A review of educational strategies to improve nurses' roles in recognizing and responding to deteriorating patients.

PubMed

Liaw, S Y; Scherpbier, A; Klainin-Yobas, P; Rethans, J-J

2011-09-01

Physiological instability leading to clinical deterioration often precedes cardiopulmonary arrest. Nurses, who have the most frequent patient contact and responsibility for ongoing monitoring of patients, play a crucial role in recognizing and responding to clinical deterioration. The importance of education in supporting such a role has been addressed in numerous studies. This study aimed to identify nurses' educational needs and explore educational strategies to enhance their ability in recognizing and managing wards with deteriorating patients. A literature search from databases (2000-2010) was undertaken to include papers that identified the educational needs of ward nurses and existing educational programmes related to the care of deteriorating patients. Twenty-six papers were included in this review. Findings identified the educational need to empower nurses with the appropriate knowledge and skills in recognizing, reporting and responding to patient deterioration. The review of existing educational programmes and their outcomes identified valuable teaching information and strategies, and areas that could be improved in meeting nurses' educational needs. The review has highlighted important aspects of patient safety in clinical deterioration that could be further addressed by educational strategies targeting the role of ward nurses. These strategies include: utilizing clinical decision-making models to develop nurses' decision making skills; developing a standardized tool for systematic nursing assessment and management of clinical deterioration; incorporating training in clinical deterioration as a core competence of pre-registered nursing education; providing vital signs training to nursing assistants; and conducting more rigorous studies to evaluate the effectiveness of the educational programmes. © 2011 The Authors. International Nursing Review © 2011 International Council of Nurses.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?†

PubMed Central

Hamaker, M. E.; Stauder, R.; van Munster, B. C.

2014-01-01

Background Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. Method The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Conclusion Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population. PMID:24458474

Basic and clinical immunology

NASA Technical Reports Server (NTRS)

Chinen, Javier; Shearer, William T.

2003-01-01

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

A pragmatic method for transforming clinical research data from the research electronic data capture "REDCap" to Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM): Development and evaluation of REDCap2SDTM.

PubMed

Yamamoto, Keiichi; Ota, Keiko; Akiya, Ippei; Shintani, Ayumi

2017-06-01

The Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM) can be used for new drug application studies as well as secondarily for creating a clinical research data warehouse to leverage clinical research study data across studies conducted within the same disease area. However, currently not all clinical research uses Clinical Data Acquisition Standards Harmonization (CDASH) beginning in the set-up phase of the study. Once already initiated, clinical studies that have not utilized CDASH are difficult to map in the SDTM format. In addition, most electronic data capture (EDC) systems are not equipped to export data in SDTM format; therefore, in many cases, statistical software is used to generate SDTM datasets from accumulated clinical data. In order to facilitate efficient secondary use of accumulated clinical research data using SDTM, it is necessary to develop a new tool to enable mapping of information for SDTM, even during or after the clinical research. REDCap is an EDC system developed by Vanderbilt University and is used globally by over 2100 institutions across 108 countries. In this study, we developed a simulated clinical trial to evaluate a tool called REDCap2SDTM that maps information in the Field Annotation of REDCap to SDTM and executes data conversion, including when data must be pivoted to accommodate the SDTM format, dynamically, by parsing the mapping information using R. We confirmed that generating SDTM data and the define.xml file from REDCap using REDCap2SDTM was possible. Conventionally, generation of SDTM data and the define.xml file from EDC systems requires the creation of individual programs for each clinical study. However, our proposed method can be used to generate this data and file dynamically without programming because it only involves entering the mapping information into the Field Annotation, and additional data into specific files. Our proposed method is adaptable not only to new drug application studies but also to all types of research, including observational and public health studies. Our method is also adaptable to clinical data collected with CDASH at the beginning of a study in non-standard format. We believe that this tool will reduce the workload of new drug application studies and will support data sharing and reuse of clinical research data in academia. Copyright © 2017 Elsevier Inc. All rights reserved.

Sarilumab for the treatment of rheumatoid arthritis.

PubMed

Cooper, Simon

2016-01-01

Simon Cooper has >18 years of global experience in the pharmaceutical industry. He joined Sanofi in July 2014 as the Vice President, Global Project Head. In his current position at Sanofi, Dr Cooper is responsible for the clinical development of sarilumab and the worldwide submission in rheumatoid arthritis. He joined Sanofi after serving as the Global Program Medical Director at Novartis since 2012. In this role, Dr Cooper acted as the clinical lead for secukinumab psoriasis submission. Prior to Novartis, Dr Cooper held various posts at Human Genome Sciences, USA, including Executive Director of Clinical Research, Senior Director of Clinical Research and Director of Clinical Research. During his tenure at Human Genome Sciences, USA, Dr Cooper was involved in the submission of belimumab leading to its approval for SLE, and was responsible for its subsequent clinical development program. Dr Cooper has also previously held positions at MedImmune Ltd, UK, Roche, Napp Pharmaceutical Research Ltd, Wyeth Research and Medeval Ltd. In these roles, his responsibilities ranged from medical oversight of clinical trials to medical support for commercial, medical affairs and business development. He received a Bachelor of Medicine and Bachelor of Surgery from University of Newcastle upon Tyne Medical School.

Clinical social networking--a new revolution in provider communication and delivery of clinical information across providers of care?

PubMed

Kolowitz, Brian J; Lauro, Gonzalo Romero; Venturella, James; Georgiev, Veliyan; Barone, Michael; Deible, Christopher; Shrestha, Rasu

2014-04-01

The adoption of social media technologies appears to enhance clinical outcomes through improved communications as reported by Bacigalupe (Fam Syst Heal 29(1):1-14, 2011). The ability of providers to more effectively, directly, and rapidly communicate among themselves as well as with patients should strengthen collaboration and treatment as reported by Bacigalupe (Fam Syst Heal 29(1):1-14, 2011). This paper is a case study in one organization's development of an internally designed and developed social technology solution termed "Unite." The Unite system combines social technologies' features including push notifications, messaging, community groups, and user lists with clinical workflow and applications to construct dynamic provider networks, simplify communications, and facilitate clinical workflow optimization. Modeling Unite as a social technology may ease adoption barriers. Developing a social network that is integrated with healthcare information systems in the clinical space opens the doors to capturing and studying the way in which providers communicate. The Unite system appears to have the potential to breaking down existing communication paradigms. With Unite, a rich set of usage data tied to clinical events may unravel alternative networks that can be leveraged to advance patient care.

A critical narrative review of transfer of basic science knowledge in health professions education.

PubMed

Castillo, Jean-Marie; Park, Yoon Soo; Harris, Ilene; Cheung, Jeffrey J H; Sood, Lonika; Clark, Maureen D; Kulasegaram, Kulamakan; Brydges, Ryan; Norman, Geoffrey; Woods, Nicole

2018-06-01

'Transfer' is the application of a previously learned concept to solve a new problem in another context. Transfer is essential for basic science education because, to be valuable, basic science knowledge must be transferred to clinical problem solving. Therefore, better understanding of interventions that enhance the transfer of basic science knowledge to clinical reasoning is essential. This review systematically identifies interventions described in the health professions education (HPE) literature that document the transfer of basic science knowledge to clinical reasoning, and considers teaching and assessment strategies. A systematic search of the literature was conducted. Articles related to basic science teaching at the undergraduate level in HPE were analysed using a 'transfer out'/'transfer in' conceptual framework. 'Transfer out' refers to the application of knowledge developed in one learning situation to the solving of a new problem. 'Transfer in' refers to the use of previously acquired knowledge to learn from new problems or learning situations. Of 9803 articles initially identified, 627 studies were retrieved for full text evaluation; 15 were included in the literature review. A total of 93% explored 'transfer out' to clinical reasoning and 7% (one article) explored 'transfer in'. Measures of 'transfer out' fostered by basic science knowledge included diagnostic accuracy over time and in new clinical cases. Basic science knowledge supported learning - 'transfer in' - of new related content and ultimately the 'transfer out' to diagnostic reasoning. Successful teaching strategies included the making of connections between basic and clinical sciences, the use of commonsense analogies, and the study of multiple clinical problems in multiple contexts. Performance on recall tests did not reflect the transfer of basic science knowledge to clinical reasoning. Transfer of basic science knowledge to clinical reasoning is an essential component of HPE that requires further development for implementation and scholarship. © 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Capturing Essential Information to Achieve Safe Interoperability

PubMed Central

Weininger, Sandy; Jaffe, Michael B.; Rausch, Tracy; Goldman, Julian M.

2016-01-01

In this article we describe the role of “clinical scenario” information to assure the safety of interoperable systems, as well as the system’s ability to deliver the requisite clinical functionality to improve clinical care. Described are methods and rationale for capturing the clinical needs, workflow, hazards, and device interactions in the clinical environment. Key user (clinician and clinical engineer) needs and system requirements can be derived from this information, therefore improving the communication from clinicians to medical device and information technology system developers. This methodology is intended to assist the health care community, including researchers, standards developers, regulators, and manufacturers, by providing clinical definition to support requirements in the systems engineering process, particularly those focusing on development of Integrated Clinical Environments described in standard ASTM F2761. Our focus is on identifying and documenting relevant interactions and medical device capabilities within the system using a documentation tool called medical device interface data sheets (MDIDSa) and mitigating hazardous situations related to workflow, product usability, data integration, and the lack of effective medical device-health information technology system integration to achieve safe interoperability. Portions of the analysis of a clinical scenario for a “Patient-controlled analgesia safety interlock” are provided to illustrate the method. Collecting better clinical adverse event information and proposed solutions can help identify opportunities to improve current device capabilities and interoperability and support a Learning Health System to improve health care delivery. Developing and analyzing clinical scenarios are the first steps in creating solutions to address vexing patient safety problems and enable clinical innovation. A web-based research tool for implementing a means of acquiring and managing this information, the Clinical Scenario Repository™, is described. PMID:27387840

Capturing Essential Information to Achieve Safe Interoperability.

PubMed

Weininger, Sandy; Jaffe, Michael B; Rausch, Tracy; Goldman, Julian M

2017-01-01

In this article, we describe the role of "clinical scenario" information to assure the safety of interoperable systems, as well as the system's ability to deliver the requisite clinical functionality to improve clinical care. Described are methods and rationale for capturing the clinical needs, workflow, hazards, and device interactions in the clinical environment. Key user (clinician and clinical engineer) needs and system requirements can be derived from this information, therefore, improving the communication from clinicians to medical device and information technology system developers. This methodology is intended to assist the health care community, including researchers, standards developers, regulators, and manufacturers, by providing clinical definition to support requirements in the systems engineering process, particularly those focusing on development of Integrated Clinical Environments described in standard ASTM F2761. Our focus is on identifying and documenting relevant interactions and medical device capabilities within the system using a documentation tool called medical device interface data sheets and mitigating hazardous situations related to workflow, product usability, data integration, and the lack of effective medical device-health information technology system integration to achieve safe interoperability. Portions of the analysis of a clinical scenario for a "patient-controlled analgesia safety interlock" are provided to illustrate the method. Collecting better clinical adverse event information and proposed solutions can help identify opportunities to improve current device capabilities and interoperability and support a learning health system to improve health care delivery. Developing and analyzing clinical scenarios are the first steps in creating solutions to address vexing patient safety problems and enable clinical innovation. A Web-based research tool for implementing a means of acquiring and managing this information, the Clinical Scenario Repository™ (MD PnP Program), is described.

Creation of a core outcome set for clinical trials of people with shoulder pain: a study protocol.

PubMed

Gagnier, Joel J; Page, Matthew J; Huang, Hsiaomin; Verhagen, Arianne P; Buchbinder, Rachelle

2017-07-20

The selection of appropriate outcomes or domains is crucial when designing clinical trials, to appreciate the effects of different interventions, pool results, and make valid comparisons between trials. If the findings are to influence policy and practice, then the chosen outcomes need to be relevant and important to key stakeholders, including patients and the public, healthcare professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. Recent reviews of the measurement properties of patient-reported outcome measures for shoulder disorders revealed a large selection of diverse measures, many with questionable validity, reliability, and responsiveness. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set (COS), which should be measured and reported in all trials of shoulder disorders. The purpose of the present project is to develop and disseminate a COS for clinical trials in shoulder disorders. The methods for the COS development will include 3 phases: (1) a comprehensive review of the core domains used in shoulder disorder trials; (2) an international Delphi study involving relevant stakeholders (patients, clinicians, scientists) to define which domains should be core; and (3) an international focus group informed by the evidence identified in phases 1 and 2, to determine which measurement instruments best measure the core domains and identification of any evidence gaps that require further empiric evidence. The aim of the current proposal is to convene several meetings of international experts and patients to develop a COS for clinical trials of shoulder disorders and to develop an implementation strategy to ensure rapid uptake of the core set of outcomes in clinical trials. There would be an expectation that the core set of outcomes would always be collected and reported, but it would not preclude use of additional outcomes in a particular trial.

FRAX(®) Clinical Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

PubMed

McCloskey, Eugene V; Binkley, Neil

2011-01-01

The World Health Organization fracture risk assessment tool, FRAX(®), is an advance in clinical care that can assist in clinical decision-making. However, with increasing clinical utilization, numerous questions have arisen regarding how to best estimate fracture risk in an individual patient. Recognizing the need to assist clinicians in optimal use of FRAX(®), the International Osteoporosis Foundation (IOF) in conjunction with the International Society for Clinical Densitometry (ISCD) assembled an international panel of experts that ultimately developed joint Official Positions of the ISCD and IOF advising clinicians regarding FRAX(®) usage. As part of the process, the charge of the FRAX(®) Clinical Task Force was to review and synthesize data surrounding a number of recognized clinical risk factors including rheumatoid arthritis, smoking, alcohol, prior fracture, falls, bone turnover markers and glucocorticoid use. This synthesis was presented to the expert panel and constitutes the data on which the subsequent Official Positions are predicated. A summary of the Clinical Task Force composition and charge is presented here. Copyright © 2011. Published by Elsevier Inc.

Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers.

PubMed

Dunnenberger, Henry M; Crews, Kristine R; Hoffman, James M; Caudle, Kelly E; Broeckel, Ulrich; Howard, Scott C; Hunkler, Robert J; Klein, Teri E; Evans, William E; Relling, Mary V

2015-01-01

Although the field of pharmacogenetics has existed for decades, practioners have been slow to implement pharmacogenetic testing in clinical care. Numerous publications describe the barriers to clinical implementation of pharmacogenetics. Recently, several freely available resources have been developed to help address these barriers. In this review, we discuss current programs that use preemptive genotyping to optimize the pharmacotherapy of patients. Array-based preemptive testing includes a large number of relevant pharmacogenes that impact multiple high-risk drugs. Using a preemptive approach allows genotyping results to be available prior to any prescribing decision so that genomic variation may be considered as an inherent patient characteristic in the planning of therapy. This review describes the common elements among programs that have implemented preemptive genotyping and highlights key processes for implementation, including clinical decision support.

The emergence of diagnostic imaging technologies in breast cancer: discovery, regulatory approval, reimbursement, and adoption in clinical guidelines.

PubMed

Gold, Laura S; Klein, Gregory; Carr, Lauren; Kessler, Larry; Sullivan, Sean D

2012-01-25

In this article, we trace the chronology of developments in breast imaging technologies that are used for diagnosis and staging of breast cancer, including mammography, ultrasonography, magnetic resonance imaging, computed tomography, and positron emission tomography. We explore factors that affected clinical acceptance and utilization of these technologies from discovery to clinical use, including milestones in peer-reviewed publication, US Food and Drug Administration approval, reimbursement by payers, and adoption into clinical guidelines. The factors driving utilization of new imaging technologies are mainly driven by regulatory approval and reimbursement by payers rather than evidence that they provide benefits to patients. Comparative effectiveness research can serve as a useful tool to investigate whether these imaging modalities provide information that improves patient outcomes in real-world settings.

Agile methods in biomedical software development: a multi-site experience report.

PubMed

Kane, David W; Hohman, Moses M; Cerami, Ethan G; McCormick, Michael W; Kuhlmman, Karl F; Byrd, Jeff A

2006-05-30

Agile is an iterative approach to software development that relies on strong collaboration and automation to keep pace with dynamic environments. We have successfully used agile development approaches to create and maintain biomedical software, including software for bioinformatics. This paper reports on a qualitative study of our experiences using these methods. We have found that agile methods are well suited to the exploratory and iterative nature of scientific inquiry. They provide a robust framework for reproducing scientific results and for developing clinical support systems. The agile development approach also provides a model for collaboration between software engineers and researchers. We present our experience using agile methodologies in projects at six different biomedical software development organizations. The organizations include academic, commercial and government development teams, and included both bioinformatics and clinical support applications. We found that agile practices were a match for the needs of our biomedical projects and contributed to the success of our organizations. We found that the agile development approach was a good fit for our organizations, and that these practices should be applicable and valuable to other biomedical software development efforts. Although we found differences in how agile methods were used, we were also able to identify a set of core practices that were common to all of the groups, and that could be a focus for others seeking to adopt these methods.

Agile methods in biomedical software development: a multi-site experience report

PubMed Central

Kane, David W; Hohman, Moses M; Cerami, Ethan G; McCormick, Michael W; Kuhlmman, Karl F; Byrd, Jeff A

2006-01-01

Background Agile is an iterative approach to software development that relies on strong collaboration and automation to keep pace with dynamic environments. We have successfully used agile development approaches to create and maintain biomedical software, including software for bioinformatics. This paper reports on a qualitative study of our experiences using these methods. Results We have found that agile methods are well suited to the exploratory and iterative nature of scientific inquiry. They provide a robust framework for reproducing scientific results and for developing clinical support systems. The agile development approach also provides a model for collaboration between software engineers and researchers. We present our experience using agile methodologies in projects at six different biomedical software development organizations. The organizations include academic, commercial and government development teams, and included both bioinformatics and clinical support applications. We found that agile practices were a match for the needs of our biomedical projects and contributed to the success of our organizations. Conclusion We found that the agile development approach was a good fit for our organizations, and that these practices should be applicable and valuable to other biomedical software development efforts. Although we found differences in how agile methods were used, we were also able to identify a set of core practices that were common to all of the groups, and that could be a focus for others seeking to adopt these methods. PMID:16734914

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment. Discussion To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety. Trial registration Eudra CT. Identifier: 2009-016643-18. PMID:23237631

Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

PubMed

Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

2013-06-01

Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

Development of a Core Clinical Dataset to Characterize Serious Illness, Injuries, and Resource Requirements for Acute Medical Responses to Public Health Emergencies.

PubMed

Murphy, David J; Rubinson, Lewis; Blum, James; Isakov, Alexander; Bhagwanjee, Statish; Cairns, Charles B; Cobb, J Perren; Sevransky, Jonathan E

2015-11-01

In developed countries, public health systems have become adept at rapidly identifying the etiology and impact of public health emergencies. However, within the time course of clinical responses, shortfalls in readily analyzable patient-level data limit capabilities to understand clinical course, predict outcomes, ensure resource availability, and evaluate the effectiveness of diagnostic and therapeutic strategies for seriously ill and injured patients. To be useful in the timeline of a public health emergency, multi-institutional clinical investigation systems must be in place to rapidly collect, analyze, and disseminate detailed clinical information regarding patients across prehospital, emergency department, and acute care hospital settings, including ICUs. As an initial step to near real-time clinical learning during public health emergencies, we sought to develop an "all-hazards" core dataset to characterize serious illness and injuries and the resource requirements for acute medical response across the care continuum. A multidisciplinary panel of clinicians, public health professionals, and researchers with expertise in public health emergencies. Group consensus process. The consensus process included regularly scheduled conference calls, electronic communications, and an in-person meeting to generate candidate variables. Candidate variables were then reviewed by the group to meet the competing criteria of utility and feasibility resulting in the core dataset. The 40-member panel generated 215 candidate variables for potential dataset inclusion. The final dataset includes 140 patient-level variables in the domains of demographics and anthropometrics (7), prehospital (11), emergency department (13), diagnosis (8), severity of illness (54), medications and interventions (38), and outcomes (9). The resulting all-hazard core dataset for seriously ill and injured persons provides a foundation to facilitate rapid collection, analyses, and dissemination of information necessary for clinicians, public health officials, and policymakers to optimize public health emergency response. Further work is needed to validate the effectiveness of the dataset in a variety of emergency settings.

Improvement in resource utilization after development of a clinical pathway for patients with pressure ulcers.

PubMed

Dzwierzynski, W W; Spitz, K; Hartz, A; Guse, C; Larson, D L

1998-11-01

Clinical pathways are interdisciplinary patient care plans intended to reduce variance and improve quality of care while lowering health care cost. This study was undertaken to determine whether the development of a clinical pathway for care of patients with pressure ulcers can indeed decrease health care costs while preserving quality of care. A clinical pathway for surgical reconstruction of pressure ulcers was developed by standardizing the current practices of our plastic surgeon group. The pathway provided direction in optimal scheduling of physician interventions along with nursing, physical and occupational therapies, and spinal cord rehabilitation interventions. It covered all potential elements of patient care, including laboratory, radiology, dietary services, intravenous fluids, and use of specialty beds. It defined patient outcomes and outlined discharge planning. Pathways were distributed throughout all services caring for patients with pressure ulcers. Patient charts and billing data were reviewed for the 16-month periods before and after initiation of the pathway. No other significant changes in treatment occurred during this time frame. Ninety-seven patient charts were examined (54 before pathway and 43 after pathway implementation). Parameters evaluated included length of stay and total charges (including bed use, medications, laboratory tests, and radiology). Patient readmission rate was also examined. A significant reduction in patient length of stay and total charges was achieved after implementation of the clinical pathway. Reduction was seen not only for patients treated with flaps by plastic surgery but also for patients with pressure ulcers who were not specifically targeted such as those from other services. The readmission rate decreased slightly, although not significantly, after the pathway inception. Total cost saving was almost $11,000 per patient (23 percent). In conclusion, implementation of a clinical pathway, because it standardizes care and reduces variations and duplication of care, can reduce health care cost without impairing quality of care in the treatment of decubitus ulcer patients.

Delivery of HIV care during the 2007 post-election crisis in Kenya: a case study analyzing the response of the Academic Model Providing Access to Healthcare (AMPATH) program

PubMed Central

2013-01-01

Background Widespread violence followed the 2007 presidential elections in Kenya resulting in the deaths of a reported 1,133 people and the displacement of approximately 660,000 others. At the time of the crisis the United States Agency for International Development-Academic Model Providing Access to Healthcare (USAID-AMPATH) Partnership was operating 17 primary HIV clinics in western Kenya and treating 59,437 HIV positive patients (23,437 on antiretroviral therapy (ART)). Methods This case study examines AMPATH’s provision of care and maintenance of patients on ART throughout the period of disruption. This was accomplished by implementing immediate interventions including rapid information dissemination through the media, emergency hotlines and community liaisons; organization of a Crisis Response leadership team; the prompt assembly of multidisciplinary teams to address patient care, including psychological support staff (in clinics and in camps for internally displaced persons (IDP)); and the use of the AMPATH Medical Records System to identify patients on ART who had missed clinic appointments. Results These interventions resulted in the opening of all AMPATH clinics within five days of their scheduled post-holiday opening dates, 23,949 patient visits in January 2008 (23,259 previously scheduled), uninterrupted availability of antiretrovirals at all clinics, treatment of 1,420 HIV patients in IDP camps, distribution of basic provisions, mobilization of outreach services to locate missing AMPATH patients and delivery of psychosocial support to 300 staff members and 632 patients in IDP camps. Conclusion Key lessons learned in maintaining the delivery of HIV care in a crisis situation include the importance of advance planning to develop programs that can function during a crisis, an emphasis on a rapid programmatic response, the ability of clinics to function autonomously, patient knowledge of their disease, the use of community and patient networks, addressing staff needs and developing effective patient tracking systems. PMID:24289095

25 CFR 700.453 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... normally found in a community and includes but is not limited to water, sewer and electrical lines, community centers, health centers and clinics, roads, and business establishments. (i) Services means activities relating to human development including, but not limited to, educational and job training, mental...

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

PubMed

Mitchell, Marc; Hedt, Bethany L; Eshun-Wilson, Ingrid; Fraser, Hamish; John, Melanie-Anne; Menezes, Colin; Grobusch, Martin P; Jackson, Jonathan; Taljaard, Jantjie; Lesh, Neal

2012-03-01

The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions. Patients visiting two ART clinics in South Africa for routine follow-up visits between March 2007 and April 2008 were included in our study. Each patient was screened by non-physician counselors using the handheld device and then received a full clinical assessment. Clinicians' report on whether full clinical assessment had been necessary was used as the gold standard for determining "required referral". Observations were randomly divided into two datasets--989 for developing a referral protocol and 200 for validating protocol performance. A third of patients had at least one physical complaint, and 16% had five or more physical complaints. 38% of patients required referral for full clinical assessment. We identify a subset of questions which are 87% sensitive and 47% specific for recommended patient referral. The final screening protocol is highly sensitive and could reduce burden on ART clinicians by 30%. The uptake and acceptance of the handheld tool to support implementation of the protocol was high. Further examination of the data reveals several important questions to include in future referral algorithms to improve sensitivity and specificity. Based on these results, we identify a refined algorithm to explore in future evaluations. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The IGNITE network: a model for genomic medicine implementation and research.

PubMed

Weitzel, Kristin Wiisanen; Alexander, Madeline; Bernhardt, Barbara A; Calman, Neil; Carey, David J; Cavallari, Larisa H; Field, Julie R; Hauser, Diane; Junkins, Heather A; Levin, Phillip A; Levy, Kenneth; Madden, Ebony B; Manolio, Teri A; Odgis, Jacqueline; Orlando, Lori A; Pyeritz, Reed; Wu, R Ryanne; Shuldiner, Alan R; Bottinger, Erwin P; Denny, Joshua C; Dexter, Paul R; Flockhart, David A; Horowitz, Carol R; Johnson, Julie A; Kimmel, Stephen E; Levy, Mia A; Pollin, Toni I; Ginsburg, Geoffrey S

2016-01-05

Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genotyping, sequencing, family history or other data) to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility. To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; www.ignite-genomics.org ) Network, comprised of six projects and a coordinating center, was established in 2013 to support the development, investigation and dissemination of genomic medicine practice models that seamlessly integrate genomic data into the electronic health record and that deploy tools for point of care decision making. IGNITE site projects are aligned in their purpose of testing these models, but individual projects vary in scope and design, including exploring genetic markers for disease risk prediction and prevention, developing tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches. This paper describes the IGNITE Network and member projects, including network structure, collaborative initiatives, clinical decision support strategies, methods for return of genomic test results, and educational initiatives for patients and providers. Clinical and outcomes data from individual sites and network-wide projects are anticipated to begin being published over the next few years. The IGNITE Network is an innovative series of projects and pilot demonstrations aiming to enhance translation of validated actionable genomic information into clinical settings and develop and use measures of outcome in response to genome-based clinical interventions using a pragmatic framework to provide early data and proofs of concept on the utility of these interventions. Through these efforts and collaboration with other stakeholders, IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice.

The Skin Cancer Objective Structured Clinical Examination (SCOSCE): A multi-institutional collaboration to develop and validate a clinical skills assessment for melanoma.

PubMed

Garg, Amit; Biello, Katie; Hoot, Joyce W; Reddy, Shalini B; Wilson, Lindsay; George, Paul; Robinson-Bostom, Leslie; Belazarian, Leah; Domingues, Erik; Powers, Jennifer; Jacob, Reza; Powers, Michael; Besen, Justin; Geller, Alan C

2015-12-01

Assessing medical students on core skills related to melanoma detection is challenging in the absence of a well-developed instrument. We sought to develop an objective structured clinical examination for the detection and evaluation of melanoma among medical students. This was a prospective cohort analysis of student and objective rater agreement on performance of clinical skills and assessment of differences in performance across 3 schools. Kappa coefficients indicated excellent agreement for 3 of 5 core skills including commenting on the presence of the moulage (k = 0.87, 95% confidence interval 0.77-0.96), obtaining a history for the moulage (k = 0.84, 95% confidence interval 0.74-0.94), and making a clinical impression (k = 0.80, 95% confidence interval 0.68-0.92). There were no differences in performance across schools with respect to 3 of 5 core skills: commenting on the presence of the moulage (P = .15), initiating a history (P = .53), and managing the suspicious lesion (P value range .07-.17). Overall, 54.2% and 44.7% of students commented on the presence of the moulage and achieved maximum performance of core skills, respectively, with no difference in performance across schools. Limitations include overall sample size of students and schools. The Skin Cancer Objective Structured Clinical Examination represents a potentially important instrument to measure students' performance on the optimal step-by-step evaluation of a melanoma. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A classification of errors in lay comprehension of medical documents.

PubMed

Keselman, Alla; Smith, Catherine Arnott

2012-12-01

Emphasis on participatory medicine requires that patients and consumers participate in tasks traditionally reserved for healthcare providers. This includes reading and comprehending medical documents, often but not necessarily in the context of interacting with Personal Health Records (PHRs). Research suggests that while giving patients access to medical documents has many benefits (e.g., improved patient-provider communication), lay people often have difficulty understanding medical information. Informatics can address the problem by developing tools that support comprehension; this requires in-depth understanding of the nature and causes of errors that lay people make when comprehending clinical documents. The objective of this study was to develop a classification scheme of comprehension errors, based on lay individuals' retellings of two documents containing clinical text: a description of a clinical trial and a typical office visit note. While not comprehensive, the scheme can serve as a foundation of further development of a taxonomy of patients' comprehension errors. Eighty participants, all healthy volunteers, read and retold two medical documents. A data-driven content analysis procedure was used to extract and classify retelling errors. The resulting hierarchical classification scheme contains nine categories and 23 subcategories. The most common error made by the participants involved incorrectly recalling brand names of medications. Other common errors included misunderstanding clinical concepts, misreporting the objective of a clinical research study and physician's findings during a patient's visit, and confusing and misspelling clinical terms. A combination of informatics support and health education is likely to improve the accuracy of lay comprehension of medical documents. Published by Elsevier Inc.

Refining prognosis in lung cancer: A report on the quality and relevance of clinical prognostic tools

PubMed Central

Mahar, Alyson L.; Compton, Carolyn; McShane, Lisa M.; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A.

2015-01-01

Introduction Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biologic, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. Methods A systematic search of the scientific literature for clinical prognostic tools in lung cancer published Jan 1, 1996-Jan 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Results Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small cell lung cancer. All tools for small cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only eleven were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision-points, and prioritized inclusion of established prognostic factors over emerging factors. Conclusions Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation. PMID:26313682

A multimedia Electronic Patient Record (ePR) system for Image-Assisted Minimally Invasive Spinal Surgery

PubMed Central

Documet, Jorge; Le, Anh; Liu, Brent; Chiu, John; Huang, HK

2009-01-01

Purpose This paper presents the concept of bridging the gap between diagnostic images and image-assisted surgical treatment through the development of a one-stop multimedia electronic patient record (ePR) system that manages and distributes the real-time multimodality imaging and informatics data that assists the surgeon during all clinical phases of the operation from planning Intra-Op to post-care follow-up. We present the concept of this multimedia ePR for surgery by first focusing on Image-Assisted Minimally Invasive Spinal Surgery as a clinical application. Methods Three clinical Phases of Minimally Invasive Spinal Surgery workflow in Pre-Op, Intra-Op, and Post Op are discussed. The ePR architecture was developed based on the three-phased workflow, which includes the Pre-Op, Intra-Op, and Post-Op modules and four components comprising of the input integration unit, fault-tolerant gateway server, fault-tolerant ePR server, and the visualization and display. A prototype was built and deployed to a Minimally Invasive Spinal Surgery clinical site with user training and support for daily use. Summary A step-by step approach was introduced to develop a multi-media ePR system for Imaging-Assisted Minimally Invasive Spinal Surgery that includes images, clinical forms, waveforms, and textual data for planning the surgery, two real-time imaging techniques (digital fluoroscopic, DF) and endoscope video images (Endo), and more than half a dozen live vital signs of the patient during surgery. Clinical implementation experiences and challenges were also discussed. PMID:20033507

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure

PubMed Central

Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Jafarinasab, Mohammad Reza; Feizi, Sepehr; Moghadam, Mohammadreza Sedighi; Jadidi, Khosrow; Babaei, Mahmoud; Shirvani, Armin; Baradaran-Rafii, Alireza; Mohammad-Rabei, Hossein; Ziaei, Hossein; Ghassemi-Broumand, Mohammad; Baher, Siamak Delfaza; Naderi, Mostafa; Panahi-Bazaz, Mahmoodreza; Zarei-Ghanavati, Siamak; Hanjani, Shahriar; Ghasemi, Hassan; Salouti, Ramin; Pakbin, Mojgan; Kheiri, Bahareh

2017-01-01

Purpose: To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. Methods: The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. Results: The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. Conclusion: Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals. PMID:28299009

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure.

PubMed

Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Jafarinasab, Mohammad Reza; Feizi, Sepehr; Moghadam, Mohammadreza Sedighi; Jadidi, Khosrow; Babaei, Mahmoud; Shirvani, Armin; Baradaran-Rafii, Alireza; Mohammad-Rabei, Hossein; Ziaei, Hossein; Ghassemi-Broumand, Mohammad; Baher, Siamak Delfaza; Naderi, Mostafa; Panahi-Bazaz, Mahmoodreza; Zarei-Ghanavati, Siamak; Hanjani, Shahriar; Ghasemi, Hassan; Salouti, Ramin; Pakbin, Mojgan; Kheiri, Bahareh

2017-01-01

To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals.

Creating an optical spectroscopy system for use in a primary care clinical setting (Conference Presentation)

NASA Astrophysics Data System (ADS)

Eshein, Adam; Nguyen, The-Quyen; Radosevich, Andrew J.; Gould, Bradley; Wu, Wenli; Konda, Vani; Yang, Leslie W.; Koons, Ann; Feder, Seth; Valuckaite, Vesta; Roy, Hemant K.; Backman, Vadim

2016-03-01

While there are a plethora of in-vivo spectroscopic techniques that have demonstrated the ability to detect a number of diseases in research trials, very few techniques have successfully become a fully realized clinical technology. This is primarily due to the stringent demands on a clinical device for widespread implementation. Some of these demands include: simple operation requiring minimal or no training, safe for in-vivo patient use, no disruption to normal clinic workflow, tracking of system performance, warning for measurement abnormality, and meeting all FDA guidelines for medical use. Previously, our group developed a fiber optic probe-based optical sensing technique known as low-coherence enhanced backscattering spectroscopy (LEBS) to quantify tissue ultrastructure in-vivo. Now we have developed this technique for the application of prescreening patients for colonoscopy in a primary care (PC) clinical setting. To meet the stringent requirements for a viable medical device used in a PC clinical setting, we developed several novel components including an automated calibration tool, optical contact sensor for signal acquisition, and a contamination sensor to identify measurements which have been affected by debris. The end result is a state-of-the-art medical device that can be realistically used by a PC physician to assess a person's risk for harboring colorectal precancerous lesions. The pilot study of this system shows great promise with excellent stability and accuracy in identifying high-risk patients. While this system has been designed and optimized for our specific application, the system and design concepts are universal to most in-vivo fiber optic based spectroscopic techniques.

Role of preliminary registry data in development of a clinical trial for an innovative device: a small but integral piece of a health policy initiative

PubMed Central

Ricci, Donald R.; de Vries, Joost; Blanc, Raphael

2017-01-01

ABSTRACT Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained. Evaluation of procedural and follow-up efficacy and safety data in a preliminary series of cases, chosen to simulate published data, allows the design and conduct of clinical trials that are required to verify preliminary observations, closing the loop on one aspect of modifying health policy decisions. PMID:28321285

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study

PubMed Central

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-01-01

Objectives Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. Setting The setting for this research was a major academic institution in Beijing, China. Participants The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Methods Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Results Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. Conclusion These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers. PMID:28928184

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study.

PubMed

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-09-18

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. The setting for this research was a major academic institution in Beijing, China. The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Limited clinical reasoning skills used by novice physiotherapists when involved in the assessment and management of patients with shoulder problems: a qualitative study

PubMed Central

May, Stephen; Withers, Sarah; Reeve, Sarah; Greasley, Alison

2010-01-01

The aim of this study was to explore the clinical reasoning process used by novice physical therapists in specific patient problems. Nine physical therapists in the UK with limited experience of managing musculoskeletal problems were included. Semi-structured interviews were conducted on how novice physical therapists would assess and manage a patient with a shoulder problem; interviews were transcribed and analyzed using framework analysis. To be included as a final theme at least 50% of participants had to mention that theme. A large number of items (n = 93) were excluded as fewer than 50% of participants referred to each item. Included items related to seven main themes: history (16), physical exam (13), investigations (1), diagnostic reasoning (1), clinical reasoning process (diagnostic pathway) (3), clinical reasoning process (management pathway) (5) and treatment options (1). Items mostly related to information gathering, although there was some use of hypothetico-deductive clinical reasoning there appeared to be limited understanding of the clinical implications of data gathered, and clinical reasoning through use of pattern recognition was minimal. Major weaknesses were apparent in the clinical reasoning skills of these novice therapists compared to previous reports of expert clinical reasoning, indicating areas for development in the education of student and junior physical therapists. PMID:21655390

Evaluation of the clinical supervision and professional development of student nurses.

PubMed

Severinsson, Elisabeth; Sand, Ase

2010-09-01

The aim of the present study was to evaluate the clinical supervision and professional development of student nurses during their undergraduate education. Nursing education has undergone radical changes as a result of improvements in the academic-based clinical education required for the Bachelor's degree. The sample consisted of student nurses (n = 147) and data were collected by means of questionnaires. The results demonstrated that the frequency of sessions and the supervision model employed influence the student nurses' professional development. Several significant correlations were found, most of which were related to the development of the student nurses' professional relationships with their supervisors and reflection on the development of their skills. From the patients' perspective, a high correlation was found between the factors 'preserving integrity' and 'protecting participation by patients and family members'. Clinical supervision strongly influences the student nurses' development of a professional identity, enhancing decision-making ability and personal growth. However, development of documentation skills should include a greater level of user involvement. The findings highlight the need for management and staff nurses to engage in on-going professional development. Transformative leadership, which is value driven, can facilitate and enhance the supervision and development of student nurses. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Questioning skills of clinical facilitators supporting undergraduate nursing students.

PubMed

Phillips, Nicole M; Duke, Maxine M; Weerasuriya, Rona

2017-12-01

To report on a study investigating questioning skills of clinical facilitators who support the learning of undergraduate nursing students. The ability to think critically is integral to decision-making and the provision of safe and quality patient care. Developing students' critical thinking skills is expected of those who supervise and facilitate student learning in the clinical setting. Models used to facilitate student learning in the clinical setting have changed over the years with clinicians having dual responsibility for patient care and facilitating student learning. Many of these nurses have no preparation for the educative role. This study adapted a comparative study conducted over fifteen years ago. Descriptive online survey including three acute care patient scenarios involving an undergraduate nursing student. Participants were required to identify the questions they would ask the student in relation to the scenario. A total of 133 clinical facilitators including clinical teachers, clinical educators and preceptors from five large partner healthcare organisations of one Australian university participated. The majority of questions asked were knowledge questions, the lowest category in the cognitive domain requiring only simple recall of information. Facilitators who had undertaken an education-related course/workshop or formal qualification asked significantly more questions from the higher cognitive level. The study provides some evidence that nursing facilitators in the clinical setting ask students predominantly low-level questions. Further research is needed to identify strategies that develop the capacity of facilitators to ask higher level cognitive questions. Clinical facilitators should undertake targeted education that focuses on how to frame questions for students that demand application, analysis, synthesis and evaluation. © 2017 John Wiley & Sons Ltd.

[The future of clinical laboratory database management system].

PubMed

Kambe, M; Imidy, D; Matsubara, A; Sugimoto, Y

1999-09-01

To assess the present status of the clinical laboratory database management system, the difference between the Clinical Laboratory Information System and Clinical Laboratory System was explained in this study. Although three kinds of database management systems (DBMS) were shown including the relational model, tree model and network model, the relational model was found to be the best DBMS for the clinical laboratory database based on our experience and developments of some clinical laboratory expert systems. As a future clinical laboratory database management system, the IC card system connected to an automatic chemical analyzer was proposed for personal health data management and a microscope/video system was proposed for dynamic data management of leukocytes or bacteria.

A Grading System To Evaluate Objectively the Strength of Pre-Clinical Data of Acute Neuroprotective Therapies for Clinical Translation in Spinal Cord Injury

PubMed Central

Okon, Elena B.; Tsai, Eve; Beattie, Michael S.; Bresnahan, Jacqueline C.; Magnuson, David K.; Reier, Paul J.; McTigue, Dana M.; Popovich, Phillip G.; Blight, Andrew R.; Oudega, Martin; Guest, James D.; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

2011-01-01

Abstract The past three decades have seen an explosion of research interest in spinal cord injury (SCI) and the development of hundreds of potential therapies that have demonstrated some promise in pre-clinical experimental animal models. A growing number of these treatments are seeking to be translated into human clinical trials. Conducting such a clinical trial, however, is extremely costly, not only for the time and money required to execute it, but also for the limited resources that will then no longer be available to evaluate other promising therapies. The decision about what therapies have sufficient pre-clinical evidence of efficacy to justify testing in humans is therefore of utmost importance. Here, we have developed a scoring system for objectively grading the body of pre-clinical literature on neuroprotective treatments for acute SCI. The components of the system include an evaluation of a number of factors that are thought to be important in considering the “robustness” of a therapy's efficacy, including the animal species and injury models that have been used to test it, the time window of efficacy, the types of functional improvements effected by it, and whether efficacy has been independently replicated. The selection of these factors was based on the results of a questionnaire that was performed within the SCI research community. A modified Delphi consensus-building exercise was then conducted with experts in pre-clinical SCI research to refine the criteria and decide upon how to score them. Finally, the grading system was applied to a series of potential neuroprotective treatments for acute SCI. This represents a systematic approach to developing an objective method of evaluating the extent to which the pre-clinical literature supports the translation of a particular experimental treatment into human trials. PMID:20507235

‘Toning’ up hypotonia assessment: A proposal and critique

PubMed Central

Joubert, Robin W.E.

2016-01-01

Background Clinical assessment of hypotonia is challenging due to the subjective nature of the initial clinical evaluation. This poses dilemmas for practitioners in gaining accuracy, given that the presentation of hypotonia can be either a non-threatening or malevolent sign. The research question posed was how clinical assessment can be improved, given the current contentions expressed in the scientific literature. Objectives This paper describes the development and critique of a clinical algorithm to aid the assessment of hypotonia. Methods An initial exploratory sequential phase, consisting of a systematic review, a survey amongst clinicians and a Delphi process, assisted in the development of the algorithm, which is presented within the framework of the International Classification of Functioning, Disability and Health. The ensuing critique followed a qualitative emergent–systematic focus group design with a purposive sample of 59 clinicians. Data were analysed using semantical content analysis and are presented thematically with analytical considerations. Results This study culminated in the development of an evidence-based clinical algorithm for practice. The qualitative critique of the algorithm considered aspects such as inadequacies, misconceptions and omissions; strengths; clinical use; resource implications; and recommendations. Conclusions The first prototype and critique of a clinical algorithm to assist the clinical assessment of hypotonia in children has been described. Barriers highlighted include aspects related to knowledge gaps of clinicians, issues around user-friendliness and formatting concerns. Strengths identified by the critique included aspects related to the evidence-based nature of the criteria within the algorithm, the suitability of the algorithm in being merged or extending current practice, the potential of the algorithm in aiding more accurate decision-making, the suitability of the algorithm across age groups and the logical flow. These findings provide a starting point towards ascertaining the clinical utility of the algorithm as an essential step towards evidence-based praxis. PMID:28730054

Adding value to clinical trial registries: insights from Australian Cancer Trials Online, a website for consumers.

PubMed

Dear, Rachel; Barratt, Alexandra; Askie, Lisa; McGeechan, Kevin; Arora, Sheena; Crossing, Sally; Currow, David; Tattersall, Martin

2011-02-01

Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use. An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries. The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov. The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers' information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users. Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided by registrants of cancer trials on ANZCTR, this can compromise the quality and usefulness of the data for the end-user, in this case consumers, as they may encounter gaps in the data. Expanding the World Health Organization Trial Registration Data Set to include this additional information, particularly the lay summary, would be valuable. A well-coordinated system of clinical trial registration is critical to the success of efforts to provide better access for all to inform about clinical trials.

Developing a unified list of physicians' reasoning tasks during clinical encounters.

PubMed

Goldszmidt, Mark; Minda, John Paul; Bordage, Georges

2013-03-01

The clinical reasoning literature focuses on how physicians reason while making decisions, rather than on what they reason about while performing their clinical tasks. In an attempt to provide a common language for discussing, teaching, and researching clinical reasoning, the authors undertook the task of developing a unified list of physicians' reasoning tasks, or what they reason about, during clinical encounters. The authors compiled an initial list of 20 reasoning tasks based on the literature from four content areas--clinical reasoning, communications, medical errors, and clinical guidelines. In the summer and fall of 2010, they surveyed a purposive sample of 46 international experts in clinical reasoning and communications. From the results of the first survey, the authors refined their list of reasoning tasks, then resurveyed 22 of the original participants. From the results of the second survey, they further refined their list and validated the inclusion of the reasoning tasks. Twenty-four of 46 (52%) and 15 of 22 (65%) participants completed the first- and second-round surveys, respectively. Following the second-round survey, the authors' list included 24 reasoning tasks, and a clinical example corresponding to each, that fell into four broad categories: framing the encounter (3), diagnosis (8), management (11), and self-reflection (2). The development of this unified list represents a first step in offering a vocabulary for discussing, reflecting on, teaching, and studying physicians' reasoning tasks during clinical encounters.

Optimization of the decision-making process for the selection of therapeutics to undergo clinical testing for spinal cord injury in the North American Clinical Trials Network.

PubMed

Guest, James; Harrop, James S; Aarabi, Bizhan; Grossman, Robert G; Fawcett, James W; Fehlings, Michael G; Tator, Charles H

2012-09-01

The North American Clinical Trials Network (NACTN) includes 9 clinical centers funded by the US Department of Defense and the Christopher Reeve Paralysis Foundation. Its purpose is to accelerate clinical testing of promising therapeutics in spinal cord injury (SCI) through the development of a robust interactive infrastructure. This structure includes key committees that serve to provide longitudinal guidance to the Network. These committees include the Executive, Data Management, and Neurological Outcome Assessments Committees, and the Therapeutic Selection Committee (TSC), which is the subject of this manuscript. The NACTN brings unique elements to the SCI field. The Network's stability is not restricted to a single clinical trial. Network members have diverse expertise and include experts in clinical care, clinical trial design and methodology, pharmacology, preclinical and clinical research, and advanced rehabilitation techniques. Frequent systematic communication is assigned a high value, as is democratic process, fairness and efficiency of decision making, and resource allocation. This article focuses on how decision making occurs within the TSC to rank alternative therapeutics according to 2 main variables: quality of the preclinical data set, and fit with the Network's aims and capabilities. This selection process is important because if the Network's resources are committed to a therapeutic, alternatives cannot be pursued. A proposed methodology includes a multicriteria decision analysis that uses a Multi-Attribute Global Inference of Quality matrix to quantify the process. To rank therapeutics, the TSC uses a series of consensus steps designed to reduce individual and group bias and limit subjectivity. Given the difficulties encountered by industry in completing clinical trials in SCI, stable collaborative not-for-profit consortia, such as the NACTN, may be essential to clinical progress in SCI. The evolution of the NACTN also offers substantial opportunity to refine decision making and group dynamics. Making the best possible decisions concerning therapeutics selection for trial testing is a cornerstone of the Network's function.

A protocol for developing, disseminating, and implementing a core outcome set for pre-eclampsia.

PubMed

Duffy, James M N; van 't Hooft, Janneke; Gale, Chris; Brown, Mark; Grobman, William; Fitzpatrick, Ray; Karumanchi, S Ananth; Lucas, Nuala; Magee, Laura; Mol, Ben; Stark, Michael; Thangaratinam, Shakila; Wilson, Mathew; von Dadelszen, Peter; Williamson, Paula; Khan, Khalid S; Ziebland, Sue; McManus, Richard J

2016-10-01

Pre-eclampsia is a serious complication of pregnancy and contributes to maternal and offspring mortality and morbidity. Randomised controlled trials evaluating therapeutic interventions for pre-eclampsia have reported many different outcomes and outcome measures. Such variation contributes to an inability to compare, contrast, and combine individual studies, limiting the usefulness of research to inform clinical practice. The development and use of a core outcome set would help to address these issues ensuring outcomes important to all stakeholders, including patients, will be collected and reported in a standardised fashion. An international steering group including healthcare professionals, researchers, and patients, has been formed to guide the development of this core outcome set. Potential outcomes will be identified through a comprehensive literature review and semi-structured interviews with patients. Potential core outcomes will be entered into an international, multi-perspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and patients will be invited to participate. The modified Delphi method encourages whole and stakeholder group convergence towards consensus 'core' outcomes. Once core outcomes have been agreed upon it is important to determine how they should be measured. The truth, discrimination, and feasibility assessment framework will assess the quality of potential outcome measures. High quality outcome measures will be associated with core outcomes. Mechanisms exist to disseminate and implement the resulting core outcome set within an international context. Embedding the core outcome set within future clinical trials, systematic reviews, and clinical practice guidelines could make a profound contribution to advancing the usefulness of research to inform clinical practice, enhance patient care, and improve maternal and offspring outcomes. The infrastructure created by developing a core outcome set for pre-eclampsia could be leveraged in other settings, for example selecting research priorities and clinical practice guideline development. PROSPECTIVE REGISTRATION: [1] Core Outcome Measures in Effectiveness Trials (COMET) registration number: 588. [2] International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42015015529. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demonstrate clinical efficacy.

PubMed

Bush, Karen; Heep, Markus; Macielag, Mark J; Noel, Gary J

2007-04-01

Ceftobiprole is the first of the investigational beta-lactam antibiotics with in vitro activity against methicillin-resistant staphylococci to reach and complete Phase III therapeutic trials. Its antibacterial spectrum includes methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, penicillin-resistant streptococci and many Gram-negative pathogens. It has demonstrated in vivo activity against many experimental infections caused by these pathogens. Ceftobiprole has completed Phase III clinical trials for complicated skin and skin structure infections, is being studied in Phase III pneumonia trials and has demonstrated non-inferiority compared with vancomycin in a Phase III complicated skin and skin structure infections trial, resulting in > 90% clinical cures of infections caused by MRSA. Other anti-MRSA beta-lactams in therapeutic clinical trials include the carbapenem CS-023/RO-4908463 and the cephalosporin ceftaroline (PPI-0903). The future of all of these agents will depend on their clinical efficacy, safety and their ability to be accepted as beta-lactams for the reliable treatment of a broad spectrum of infections, including those caused by MRSA.

[Clinical manifestations of neurocysticercosis].

PubMed

San-juan Orta, D

2009-06-01

Cysticercosis is a common parasitic infection caused by the larval phase of the Taenia solium, it infects humans as well as pigs. Considered an endemic parasitosis in developing countries including Latin America, Asia and Africa. Clinical manifestations of the disease can be influenced by ambient factors, host individualities and the infectious agent itself. Neurocysticercosis can be asymptomatic or present with various signs and symptoms that can vary in severity. This review is focused on analyzing the various presentations of Neurocysticercosis throughout different age groups, and special populations. We found asymptomatic presentations to be the most common form, followed by various grades of severity including in its most severe form death. The most common alterations include: epilepsy (60-90%), intracraneal hypertension (14-27%), as well as neuropsychiatric symptoms (5-52%), and focal neurological deficits (4-19%). The heterogeneity of the clinical scenario relies upon parasite factors (number, localization and stage of central nervous system [CNS] disease), host particularities (gender, age and immunologic response), and finally environmental factors. The most common form of infection is asymptomatic although there are various forms of clinical manifestations that rely upon different factors including environment, host response and the parasite itself.

A rapid evidence-based service by librarians provided information to answer primary care clinical questions.

PubMed

McGowan, Jessie; Hogg, William; Rader, Tamara; Salzwedel, Doug; Worster, Danielle; Cogo, Elise; Rowan, Margo

2010-03-01

A librarian consultation service was offered to 88 primary care clinicians during office hours. This included a streamlined evidence-based process to answer questions in fewer than 20 min. This included a contact centre accessed through a Web-based platform and using hand-held devices and computers with Web access. Librarians were given technical training in evidence-based medicine, including how to summarise evidence. To describe the process and lessons learned from developing and operating a rapid response librarian consultation service for primary care clinicians. Evaluation included librarian interviews and a clinician exit satisfaction survey. Clinicians were positive about its impact on their clinical practice and decision making. The project revealed some important 'lessons learned' in the clinical use of hand-held devices, knowledge translation and training for clinicians and librarians. The Just-in-Time Librarian Consultation Service showed that it was possible to provide evidence-based answers to clinical questions in 15 min or less. The project overcame a number of barriers using innovative solutions. There are many opportunities to build on this experience for future joint projects of librarians and healthcare providers.

Dual-Energy CT: New Horizon in Medical Imaging

PubMed Central

Goo, Jin Mo

2017-01-01

Dual-energy CT has remained underutilized over the past decade probably due to a cumbersome workflow issue and current technical limitations. Clinical radiologists should be made aware of the potential clinical benefits of dual-energy CT over single-energy CT. To accomplish this aim, the basic principle, current acquisition methods with advantages and disadvantages, and various material-specific imaging methods as clinical applications of dual-energy CT should be addressed in detail. Current dual-energy CT acquisition methods include dual tubes with or without beam filtration, rapid voltage switching, dual-layer detector, split filter technique, and sequential scanning. Dual-energy material-specific imaging methods include virtual monoenergetic or monochromatic imaging, effective atomic number map, virtual non-contrast or unenhanced imaging, virtual non-calcium imaging, iodine map, inhaled xenon map, uric acid imaging, automatic bone removal, and lung vessels analysis. In this review, we focus on dual-energy CT imaging including related issues of radiation exposure to patients, scanning and post-processing options, and potential clinical benefits mainly to improve the understanding of clinical radiologists and thus, expand the clinical use of dual-energy CT; in addition, we briefly describe the current technical limitations of dual-energy CT and the current developments of photon-counting detector. PMID:28670151

Ambiguity Within Nursing Practice: An Evolutionary Concept Analysis.

PubMed

McMahon, Michelle A; Dluhy, Nancy M

2017-02-01

To analyze the concept of ambiguity in a nursing context. Ambiguity is inherent within nursing practice. As health care becomes increasingly complex, nurses must continue to successfully deal with greater amounts of clinical ambiguity. Although ambiguity is discussed in nursing, minimal concept refinement exists to capture the contextual intricacies from a nursing lens. Nurse perception of an ambiguous clinical event, in combination with nurse tolerance level for ambiguity, can impact nurse response. Yet, little is known about what constitutes ambiguity within nursing practice (AWNP). Rodgers evolutionary method was used to explore AWNP, with emphasis on nurse thinking during ambiguous clinical situations. Literature searches across multiple databases yielded 38 articles for analysis. Attributes of AWNP include (a) variations in cues/available information, (b) multiple interpretations, (c) novel/nonroutine presentations, and (d) unpredictable. Antecedents include (a) a context-specific, clinical situation with ambiguous features needing evaluation and (b) an individual to sense a knowledge gap or perceive ambiguity. Consequences include ranges of (a) emotional, (b) behavioral, and (c) cognitive clinician responses. Preliminary findings support AWNP as a distinct concept in which ambiguity perceived by the nurse likely affects judgment, decision making, and clinical interventions. AWNP is a clinically relevant concept requiring continued development.

Long-acting injectable hormonal dosage forms for contraception.

PubMed

Wu, Linfeng; Janagam, Dileep R; Mandrell, Timothy D; Johnson, James R; Lowe, Tao L

2015-07-01

Although great efforts have been made to develop long-acting injectable hormonal contraceptives for more than four decades, few long-acting injectable contraceptives have reached the pharmaceutical market or even entered clinical trials. On the other hand, in clinical practice there is an urgent need for injectable long-acting reversible contraceptives which can provide contraceptive protection for more than 3 months after one single injection. Availability of such products will offer great flexibility to women and resolve certain continuation issues currently occurring in clinics. Herein, we reviewed the strategies exploited in the past to develop injectable hormonal contraceptive dosages including drug microcrystal suspensions, drug-loaded microsphere suspensions and in situ forming depot systems for long-term contraception and discussed the potential solutions for remaining issues met in the previous development.

[JUSTIFICATION OF USING EQUIVALENCE OF THE INDICES OF QUALITY, SAFETY, AND EFFICACY IN DEVELOPING BIOANALOGS].

PubMed

Niyazov, R R; Goryachev, D V; Gavrishina, E V; Romodanovskii, D P; Dranitsyna, M A

2015-01-01

We describe general principles of demonstrating biosimilarity, as well as selecting the biosimilarity margins. Any change in the structure of a biological molecule can modify its functional activity. Therefore, therapeutic equivalence between a biosimilar product and the corresponding reference product cannot be demonstrated using a single criterion. To demonstrate biosimilarity between two medicinal products, their various characteristics have to be evaluated which may, directly or indirectly, justify that clinically significant differences are absent. Insufficient understanding of 6ritical quality attributes brings a risk for the biosimilar product developer. This will either increase the number of non-clinical and clinical tests and trials needed or will result in awareness that the manufacturing process needs to be improved at the late stages of development, after investing significant resources in the development process. At the same time, the specification of the biological medicinal product cannot solely ensure safety and efficacy thereof. Properly characterized and controlled manufacturing process, which ensures consistency in its attributes not adequately controlled in specifications but influencing safety and efficacy profiles and showing their relevance in non-clinical tests and clinical trials, is an additional quality assurance factor. Justification of all development strategy details, including biosimilarity margins, has to be provided each time when the development process is initiated or when proceeding to the next steps. All problems encountered by the developer have to be resolved in close communication with the regulatory authority. In order to increase the quality of investigation and developer's adherence to good practices, clinical trial results should be published in detail.

Clinical trials update: highlights of the scientific sessions of the American Heart Association year 2000: Val HeFT, COPERNICUS, MERIT, CIBIS-II, BEST, AMIOVIRT, V-MAC, BREATHE, HEAT, MIRACL, FLORIDA, VIVA and the first human cardiac skeletal muscle myoblast transfer for heart failure.

PubMed

Thackray, S D; Witte, K K; Khand, A; Dunn, A; Clark, A L; Cleland, J G

2001-01-01

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at scientific sessions of the American Heart Association in November 2000. Clinical studies of particular interest to people caring for patients with heart failure include Val-HeFT, AMIOVIRT and V-MAC. New data from beta-blockers trials are reviewed, highlights from some important developments in post-infarction care, including MIRACL and FLORIDA, discussed and results of some early studies of gene therapy reported.

CURRENT CONCEPTS OF PLYOMETRIC EXERCISE.

PubMed

Davies, George; Riemann, Bryan L; Manske, Robert

2015-11-01

As knowledge regarding rehabilitation science continues to increase, exercise programs following musculoskeletal athletic injury continue to evolve. Rehabilitation programs have drastically changed, especially in the terminal phases of rehabilitation, which include performance enhancement, development of power, and a safe return to activity. Plyometric exercise has become an integral component of late phase rehabilitation as the patient nears return to activity. Among the numerous types of available exercises, plyometrics assist in the development of power, a foundation from which the athlete can refine the skills of their sport. Therefore, the purpose of this clinical commentary is to provide an overview of plyometrics including: definition, phases, the physiological, mechanical and neurophysiological basis of plyometrics, and to describe clinical guidelines and contraindications for implementing plyometric programs.

Spotlight on fluticasone furoate/umeclidinium/vilanterol in COPD: design, development, and potential place in therapy.

PubMed

Lal, Chitra; Strange, Charlie

2017-01-01

COPD is characterized by persistent airflow obstruction caused by exposure to irritants including cigarette smoke, dust, and fumes. According to the latest GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines, a combination of inhaled corticosteroids, long-acting β 2 agonists, and long-acting muscarinic receptor antagonists can be used for group D COPD patients who are at high risk for exacerbations. Umeclidinium/fluticasone furoate/vilanterol is one such triple-combination therapy currently under development with some completed and several ongoing clinical trials. This review paper summarizes the pharmacologic profiles of these medications and highlights findings from clinical trials, including safety and efficacy data, while speculating on the role of this therapy in current treatment for COPD.

Radiological clinical trials: Proposal of a problem-finding questionnaire to improve study success.

PubMed

Valdora, Francesca; Bignotti, Bianca; Calabrese, Massimo; Houssami, Nehmat; Tagliafico, Alberto

2016-12-26

To develop a survey to help define the main problems in radiological clinical trials. Since 2006, we have managed seven different radiological clinical trials recruiting patients in academic and non-academic centres. We developed a preliminary questionnaire using a four-round Delphi approach to identify problems occurring in radiological clinical trials run at our centre. We investigated the recruitment experience, involvement of all multi-disciplinary team members and main obstacles to completing the projects. A final round of Delphi processes elucidated solutions to the identified problems. Among 19/20 (95%) respondents, 10 (53%) were young physicians (under 35 years old), and the respondents included non-faculty members, fellows, residents, and undergraduate students. Ninety-four percent (18/19) of respondents showed interest in conducting clinical trials. On a scale of 1 to 10, the problems with higher/worse scores (8-9) were related to technical or communication problems. The most frequent problems across all studies were technical problems related to clinical trial equipment, insufficient willingness to participate, obstacles to understanding the design of electronic-case report form and extra work. The developed questionnaire identified the main recurring problems in radiological clinical trials as perceived by end-users and helped define possible solutions that are mostly related to having dedicated clinical trial research staff.

Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance.

PubMed

Barber, Thomas M; Dimitriadis, George K; Andreou, Avgi; Franks, Stephen

2016-06-01

Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. Accordingly, PCOS often becomes manifest in those women who carry a genetic predisposition to its development, and who also gain weight. The role of weight gain and obesity in the development of PCOS is mediated at least in part, through worsening of insulin resistance. Compensatory hyperinsulinaemia that develops in this context disrupts ovarian function, with enhanced androgen production and arrest of ovarian follicular development. Insulin resistance also contributes to the strong association of PCOS with adverse metabolic risk, including dysglycaemia, dyslipidaemia and fatty liver. Conversely, modest weight loss of just 5% body weight with improvement in insulin sensitivity, frequently results in clinically meaningful improvements in hyperandrogenic, reproductive and metabolic features. Future developments of novel therapies for obese women with PCOS should focus on promotion of weight loss and improvement in insulin sensitivity. In this context, therapies that complement lifestyle changes such as dietary modification and exercise, particularly during the maintenance phase of weight loss are important. Putative novel targets for therapy in PCOS include human brown adipose tissue. © 2016 Royal College of Physicians.

Identification of Drug Characteristics for Implementing Multiregional Clinical Trials Including Japan.

PubMed

Rokuda, Mitsuhiro; Matsumaru, Naoki; Tsukamoto, Katsura

2018-02-01

Multiregional clinical trials (MRCT) are a standard strategy used to improve global drug approval efficiency and the feasibility of clinical trials. Japan is the world's third largest drug market with a unique health care system, making it a key inclusion as an operational region for MRCT (MRCT-JP) for global drug development. We aimed to identify the factors required for efficient drug development by comprehensively reviewing the clinical trials of drugs approved in Japan to identify the factors associated with whether or not MRCT-JP is implemented. We surveyed the review reports and summaries of application data published by the Pharmaceuticals and Medical Devices Agency. We identified drugs for which the clinical trial data package included MRCT-JP and selected the same number of drugs for which the clinical trial data package did not include MRCT-JP from the most recent survey period for comparison. We also examined other publication information, in addition to the review reports, as necessary. The influence of each explanatory variable was analyzed by logistic regression analysis, with whether or not MRCT-JP was implemented as the explanatory variable. Statistical significance was set at 5%. In the survey period up to September 2017, 165 drugs developed with MRCT-JP were approved for manufacture and sale in Japan. "Respiratory system," "inhalation," "biological drug," and "under review" evaluation status for the United States, European Union, and other areas, "approved" evaluation status for the United States, "new ingredients," "priority review," "non-Japanese firm," and "Top 1-10" and "Top 11-20" drug sales rankings for pharmaceutical companies were identified as potential factors leading to the implementation of MRCT-JP. In contrast, "general anti-infectives for systemic use," "various," "external," "chemical compound," "unsubmitted" evaluation status for both the United States and European Union, and "Top 51+" drug sales rankings were potential factors for not implementing MRCT-JP. Therapeutic classification and agent type, in addition to capital type and United States and European Union evaluation status suggested by a previous study, were associated with implementing MRCT-JP. It is important to determine the best way to utilize MRCT-JP to maximize the value of products. Our findings were based on successful cases and may therefore be helpful for designing clinical development plans. Appropriate use of MRCT-JP will improve productivity in the pharmaceutical industry. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Analyzing clinical phonological data using Phon

PubMed Central

McAllister Byun, Tara

2016-01-01

In this paper, we describe how Phon, a software program for the transcription and analysis of phonological data, can be applied to facilitate clinical phonological analyses. We begin with a summary of the types of analyses that are frequently used in the assessment and management of speech sound disorders. We then discuss challenges inherent to the transcription and analysis of clinical phonological data. For each challenge, we discuss solutions currently available within Phon, and offer an outlook on future methodological and technical developments in the area of clinical phonology. This paper includes a step-by-step introduction to Phon suitable for readers who lack previous experience with the software. We conclude with a discussion of data sharing and its vital role in advancing research and intervention practices in the area of speech development and disorders. PMID:27111269

Imaging macrophages with nanoparticles

NASA Astrophysics Data System (ADS)

Weissleder, Ralph; Nahrendorf, Matthias; Pittet, Mikael J.

2014-02-01

Nanomaterials have much to offer, not only in deciphering innate immune cell biology and tracking cells, but also in advancing personalized clinical care by providing diagnostic and prognostic information, quantifying treatment efficacy and designing better therapeutics. This Review presents different types of nanomaterial, their biological properties and their applications for imaging macrophages in human diseases, including cancer, atherosclerosis, myocardial infarction, aortic aneurysm, diabetes and other conditions. We anticipate that future needs will include the development of nanomaterials that are specific for immune cell subsets and can be used as imaging surrogates for nanotherapeutics. New in vivo imaging clinical tools for noninvasive macrophage quantification are thus ultimately expected to become relevant to predicting patients' clinical outcome, defining treatment options and monitoring responses to therapy.

Healthcare provider education to support integration of pharmacogenomics in practice: the eMERGE Network experience

PubMed Central

Rohrer Vitek, Carolyn R; Abul-Husn, Noura S; Connolly, John J; Hartzler, Andrea L; Kitchner, Terrie; Peterson, Josh F; Rasmussen, Luke V; Smith, Maureen E; Stallings, Sarah; Williams, Marc S; Wolf, Wendy A; Prows, Cynthia A

2017-01-01

Ten organizations within the Electronic Medical Records and Genomics Network developed programs to implement pharmacogenomic sequencing and clinical decision support into clinical settings. Recognizing the importance of informed prescribers, a variety of strategies were used to incorporate provider education to support implementation. Education experiences with pharmacogenomics are described within the context of each organization's prior involvement, including the scope and scale of implementation specific to their Electronic Medical Records and Genomics projects. We describe common and distinct education strategies, provide exemplars and share challenges. Lessons learned inform future perspectives. Future pharmacogenomics clinical implementation initiatives need to include funding toward implementing provider education and evaluating outcomes. PMID:28639489

Patterns of Clinical Reasoning in Physical Therapist Students.

PubMed

Gilliland, Sarah; Wainwright, Susan Flannery

2017-05-01

Clinical reasoning is a complex, nonlinear problem-solving process that is influenced by models of practice. The development of physical therapists' clinical reasoning abilities is a crucial yet underresearched aspect of entry-level (professional) physical therapist education. The purpose of this qualitative study was to examine the types of clinical reasoning strategies physical therapist students engage in during a patient encounter. A qualitative descriptive case study design involving within and across case analysis was used. Eight second-year, professional physical therapist students from 2 different programs completed an evaluation and initial intervention for a standardized patient followed by a retrospective think-aloud interview to explicate their reasoning processes. Participants' clinical reasoning strategies were examined using a 2-stage qualitative method of thematic analysis. Participants demonstrated consistent signs of development of physical therapy-specific reasoning processes, yet varied in their approach to the case and use of reflection. Participants who gave greater attention to patient education and empowerment also demonstrated greater use of reflection-in-action during the patient encounter. One negative case illustrates the variability in the rate at which students may develop these abilities. Participants demonstrated development toward physical therapist--specific clinical reasoning, yet demonstrated qualitatively different approaches to the patient encounter. Multiple factors, including the use of reflection-in-action, may enable students to develop greater flexibility in their reasoning processes. © 2017 American Physical Therapy Association

Fostering interprofessional learning in a rehabilitation setting: development of an interprofessional clinical learning unit.

PubMed

Vanderzalm, Jeanne; Hall, Mark D; McFarlane, Lu-Anne; Rutherford, Laurie; Patterson, Steven K

2013-01-01

The development and implementation of interprofessional (IP) clinical learning units as a method to enhance IP clinical education and improve patient care in a rehabilitation setting are described. Using a community-based participatory research approach, academia and healthcare delivery agencies formed a partnership to create an IP clinical learning unit in a rehabilitation setting. Preimplementation data from surveys and focus group data identified areas for improvement to enhance IP understanding and collaboration. A working group developed and implemented initiatives to enhance IP practice. Preimplementation, eight themes emerged from which the working group identified goals and implemented strategies to strengthen IP learning. Goals included Creation of an IP Learning Environment, Increased Awareness of IP Practice, Role Clarification, Enhanced IP Communication, and Reflection and Evaluation. Postimplementation data revealed six themes: Communication, Informal IP Learning, Role Awareness, Positive Learning Environment, Logistics, and Challenges. The development of the IP clinical learning unit was successful and rewarding, but not without its challenges. Formal IP education was necessary to enhance collaborative practice, even in a multidisciplinary environment. Commitment and support from all participants, particularly managers and administrators from the healthcare agency, were critical to success. The focus of this unit was on a stroke rehabilitation unit; however, the development and implementation principles identified may be applicable to any team-based clinical setting. © 2013 Association of Rehabilitation Nurses.

The learning environment in professional doctorate and postgraduate dental education: a qualitative study.

PubMed

Subramanian, J; Thomson, W M

2017-11-01

Currently, there is a lack of studies focusing on professional doctoral students' and graduates' perceptions of their learning environment, in particular, using a qualitative approach to elicit in-depth information. This article aims to contribute to the existing body of knowledge by systematically exploring, critically analysing and getting a deeper understanding of professional doctorate dental students' and graduates' insights into effective and ineffective clinical and physical learning environment characteristics. The study included a total of 20 participants. Participants included 16 final-year Doctor of Clinical Dentistry (DClinDent) students and four dental specialists (graduates of the DClinDent programme). Semi-structured, individual interviews were used. Participants were asked to reflect upon and describe in detail their effective and ineffective learning environment experiences. The critical incident technique was used to guide the data collection. Data were analysed using a general inductive qualitative approach. Learning environment characteristics which participants associated with effective learning included the following: sufficient opportunities for comprehensive treatment planning; introduction to a number of patient treatment philosophies; a sufficient number of complex cases; clinically oriented research and assignment topics; a focus on clinical training in the programme generally; a research topic of a realistic depth and breadth, suitable for their 'specialist training' degree; and a well-resourced and updated physical infrastructure. On the other hand, most participants indicated that the absence of an adequate number of clinical cases, an overemphasis on research (as opposed to clinical practice) in the DClinDent programme and an 'outdated' physical infrastructure in the dental school clinics could hamper effective clinical learning. These findings contribute to the meaningful advancement of the literature on learning environment strategies through the exploration of (and in-depth qualitative insights into) what facilitated effective learning by New Zealand professional doctorate candidates and graduates. These findings provide a starting point for reflection by international academic directors, educational developers, curriculum planners, programme managers and clinical teachers in respect of the further development of the learning environment. Although the findings from this study may not be directly transferable to all international contexts, they have the potential to contribute to the further development of theory in this area. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies

PubMed Central

Abu-Shakra, M; Buskila, D; Ehrenfeld, M; Conrad, K; Shoenfeld, Y

2001-01-01

OBJECTIVES—To review the autoimmune and rheumatic manifestations of patients with malignancy.
METHODS—A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes.
RESULTS—Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy.
CONCLUSION—Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

 PMID:11302861

Automated analysis of free speech predicts psychosis onset in high-risk youths

PubMed Central

Bedi, Gillinder; Carrillo, Facundo; Cecchi, Guillermo A; Slezak, Diego Fernández; Sigman, Mariano; Mota, Natália B; Ribeiro, Sidarta; Javitt, Daniel C; Copelli, Mauro; Corcoran, Cheryl M

2015-01-01

Background/Objectives: Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals. AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis. Methods: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed. Results: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms. Conclusions: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry. PMID:27336038

A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis.

PubMed

Younossi, Zobair M; Page, Sandra; Rafiq, Nila; Birerdinc, Aybike; Stepanova, Maria; Hossain, Noreen; Afendy, Arian; Younoszai, Zahra; Goodman, Zachary; Baranova, Ancha

2011-04-01

Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis. This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables. Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated. Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65-M30 (necrosis) [AUC: 0.81, 95% CI, 0.70-0.89, 300 p value <9E 301 (-06)]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68-0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70-0.89; p value, 0.000062]. This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.

The benefits and challenges of using computer-assisted symptom assessments in oncology clinics: results of a qualitative assessment.

PubMed

Mark, Tami L; Johnson, Gina; Fortner, Barry; Ryan, Katheryn

2008-10-01

Developed for clinical use in oncology settings, the Patient Assessment, Care & Education (PACE) System is a computer technology tool designed to address the under-identification and treatment of chemotherapy-related symptoms. This system includes general core questions together with the Patient Care Monitor (PCM), a validated questionnaire that assesses patient-reported problems, six symptom burden indices, and one global quality of life index. The system automatically scores the PCM and generates a written report. The objective of this study was to assess the manner in which clinicians use this system and identify the benefits and challenges that oncology clinics may face when adopting this system. The study was part of a larger evaluation of the system that included standardized surveys and chart review. Sixteen providers (physicians, nurses, and physician assistants) at 13 community oncology clinics participated in a 30-minute interview. Responses were coded according to common phrases or concepts. Clinicians indicated that they use the system mainly for symptom assessment or review of systems. The most common benefits identified included the improved ability to identify under-reported symptoms, enhanced communication with patients; increased efficiency; and its ability to highlight patients' most bothersome symptoms. Challenges included patient burden from the frequent need to answer the questionnaires, issues with the wording and formatting of the screening questionnaire, and technical difficulties. In sum, these interviews suggest that electronic symptom assessments offer potential advantages in terms improving the integration of routine assessment of patients' symptoms and health-related quality of life into the daily flow of an oncology clinic. The approach should receive additional research and development attention.

Catheter‐associated venous air embolism in hospitalized horses: 32 cases

PubMed Central

McKenzie, Harold C.; Barton, Michelle H.; Davis, Jennifer L.; Dunkel, Bettina; Johnson, Amy L.; MacDonald, Elizabeth S.

2018-01-01

Background Venous air embolism is a potentially life‐threatening complication of IV catheter use in horses. Despite widespread anecdotal reports of their occurrence, few cases have been reported in the literature and the prognosis is currently unknown. Hypothesis/Objectives Our objective was to describe the surrounding circumstances, clinical signs, treatment, progression, and outcome of venous air embolism in hospitalized horses. Animals Thirty‐two horses with acute onset of compatible clinical signs associated with IV catheter disconnection or damage. Methods Multicenter retrospective study. Data extracted from clinical records included signalment, presenting complaint, catheter details, clinical signs, treatments, and outcome. Results Most cases resulted from extension set disconnection occurring within approximately 24 hours after catheter placement. In fewer horses, extension set damage was cited as a cause. Common clinical signs included tachycardia, tachypnea, recumbency, muscle fasciculations and agitation, with abnormal behavior including kicking and flank biting. Less commonly, pathological arrhythmias or more severe neurologic signs, including blindness and seizures, were noted. Progression was unpredictable, with some affected horses developing delayed‐onset neurologic signs. Mortality was 6/32 (19%), including 2 cases of sudden death and other horses euthanized because of persistent neurologic deficits. Negative outcomes were more common in horses with recorded blindness, sweating or recumbency, but blindness resolved in 5/8 affected horses. Conclusions and Clinical Importance The prognosis for resolution of clinical signs after air embolism is fair, but permanent neurologic deficits or pathologic cardiac arrhythmias can arise. Unpredictable progression warrants close monitoring. Systematic clinic‐based surveillance could provide additional useful information to aid prevention. PMID:29460300

International models of investigator-initiated trials: implications for Japan

PubMed Central

Trimble, E. L.; Ledermann, J.; Law, K.; Miyata, T.; Imamura, C. K.; Nam, B.-H.; Kim, Y.H.; Bang, Y.-J.; Michaels, M.; Ardron, D.; Amano, S.; Ando, Y.; Tominaga, T.; Kurokawa, K.; Takebe, N.

2012-01-01

Background Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. Materials In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. Results In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. Conclusions To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval. PMID:22843420

Implementing Clinical Research Using Factorial Designs: A Primer.

PubMed

Baker, Timothy B; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin; Mermelstein, Robin; Fiore, Michael C; Piper, Megan E; Collins, Linda M

2017-07-01

Factorial experiments have rarely been used in the development or evaluation of clinical interventions. However, factorial designs offer advantages over randomized controlled trial designs, the latter being much more frequently used in such research. Factorial designs are highly efficient (permitting evaluation of multiple intervention components with good statistical power) and present the opportunity to detect interactions amongst intervention components. Such advantages have led methodologists to advocate for the greater use of factorial designs in research on clinical interventions (Collins, Dziak, & Li, 2009). However, researchers considering the use of such designs in clinical research face a series of choices that have consequential implications for the interpretability and value of the experimental results. These choices include: whether to use a factorial design, selection of the number and type of factors to include, how to address the compatibility of the different factors included, whether and how to avoid confounds between the type and number of interventions a participant receives, and how to interpret interactions. The use of factorial designs in clinical intervention research poses choices that differ from those typically considered in randomized clinical trial designs. However, the great information yield of the former encourages clinical researchers' increased and careful execution of such designs. Copyright © 2017. Published by Elsevier Ltd.

Mentor relationship as a tool of professional development of student nurses in clinical practice.

PubMed

Saarikoski, Mikko

2003-09-01

This is a condensed version of a research project relating to the design and the development of a research instrument concerning 'Mentor Relationship as a Tool of Professional Development of Student Nurses in Clinical Practice'. This short research paper is taken from and reproduces the research work undertaken by Saarikoski (2002). The main themes refer to: (1) Evaluation scale to assess the quality of clinical learning environment and (2) Supervision of student nurses during their clinical placements. Parts one and two are taken from the main research study and include the following (i) developing and testing an evaluation tool (ii) describing how nursing students experience their clinical learning environment and (iii) the supervision given by qualified staff nurses working in a hospital setting. This abridged report discusses the methodology approaches undertaken by the author and includes: (a) comparative phased twin centred study (b) a pilot scheme and (c) a primary research instrument that was developed into an extensively validated assessment-measuring tool. This report strongly suggests that there is clear evidence in this research report that the supervisory relationship is the most important single element of pedagogical activities of staff nurses. The total satisfaction of students correlated most clearly with the method of supervision and that those satisfied students had a successful mentor relationship and frequently enough access to private supervision sessions with mentor. In the sample of this empirical study (n = 279 student nurses in Finland) individualized supervision system was most common on psychiatric wards. All nurse educators and clinical practitioners working across Europe and around the World in clinical learning environments will find this paper very useful in helping them to improve and quantify the supervisory process. This study starts bridging the gap between using and integrating both at a National and European level qualitative assessment systems that relate to the learning and supervisory process. The study encourages the need for professionals to test these new instruments in other nursing cultures and reflects upon the need for further research work in this area.

Predictors of the development of myocarditis or acute renal failure in patients with leptospirosis: An observational study

PubMed Central

2012-01-01

Background Leptospirosis has a varied clinical presentation with complications like myocarditis and acute renal failure. There are many predictors of severity and mortality including clinical and laboratory parameters. Early detection and treatment can reduce complications. Therefore recognizing the early predictors of the complications of leptospirosis is important in patient management. This study was aimed at determining the clinical and laboratory predictors of myocarditis or acute renal failure. Methods This was a prospective descriptive study carried out in the Teaching Hospital, Kandy, from 1st July 2007 to 31st July 2008. Patients with clinical features compatible with leptospirosis case definition were confirmed using the Microscopic Agglutination Test (MAT). Clinical features and laboratory measures done on admission were recorded. Patients were observed for the development of acute renal failure or myocarditis. Chi-square statistics, Fisher's exact test and Mann-Whitney U test were used to compare patients with and without complications. A logistic regression model was used to select final predictor variables. Results Sixty two confirmed leptospirosis patients were included in the study. Seven patients (11.3%) developed acute renal failure and five (8.1%) developed myocarditis while three (4.8%) had both acute renal failure and myocarditis. Conjunctival suffusion - 40 (64.5%), muscle tenderness - 28 (45.1%), oliguria - 20 (32.2%), jaundice - 12 (19.3%), hepatomegaly - 10 (16.1%), arrhythmias (irregular radial pulse) - 8 (12.9%), chest pain - 6 (9.7%), bleeding - 5 (8.1%), and shortness of breath (SOB) 4 (6.4%) were the common clinical features present among the patients. Out of these, only oliguria {odds ratio (OR) = 4.14 and 95% confidence interval (CI) 1.003-17.261}, jaundice (OR = 5.13 and 95% CI 1.149-28.003), and arrhythmias (OR = 5.774 and 95% CI 1.001-34.692), were predictors of myocarditis or acute renal failure and none of the laboratory measures could predict the two complications. Conclusions This study shows that out of clinical and laboratory variables, only oliguria, jaundice and arrhythmia are strong predictors of development of acute renal failure or myocarditis in patients with leptospirosis presented to Teaching Hospital of Kandy, Sri Lanka. PMID:22243770